A Phase 2 interventional study of Pertuzumab and Trastuzumab Fixed-Dose Combination for Subcutaneous Administration (PH FDC SC) and Pertuzumab IV in HER2-Positive Early Breast Cancer, sponsored by Hoffmann-La Roche. Completed at 40 sites in 17 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-01-02.
Sponsored by Hoffmann-La Roche · Phase 2, Interventional, and Treatment
This is a Phase II, randomized, multicentre, multinational, open-label, cross-over study in adult patients who have completed neoadjuvant chemotherapy with neoadjuvant pertuzumab and trastuzumab and have undergone surgical treatment of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. The study will consist of two adjuvant treatment periods: a treatment cross-over period and a treatment continuation period. It will evaluate participant-reported preference for a subcutaneously administered fixed-dose combination formulation (FDC SC) of pertuzumab and trastuzumab compared with intravenously (IV) administered pertuzumab and trastuzumab formulations. The study will also evaluate participant-reported satisfaction with pertuzumab and trastuzumab FDC SC and health-related quality of life outcomes; healthcare professionals' perceptions of time/resource use and convenience of pertuzumab and trastuzumab FDC SC compared with pertuzumab and trastuzumab IV formulations; as well as the safety and efficacy of each study regimen.
14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.
This study's enrollment of 160 is above the median of 72 across 10,896 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Hoffmann-La Roche is the lead sponsor of 2,101 studies on the registry; 87 are open to participants now.
Of its 330 completed or terminated interventional studies of FDA-regulated products, 248 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Disease-specific criteria:
General criteria:
Exclusion Criteria:
Cancer-specific criteria:
General criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
In the Treatment Cross-Over Period of the study, participants randomized to Arm A first received pertuzumab IV and trastuzumab IV (P+H IV) administration for 3 treatment cycles followed by the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.
Drug: Pertuzumab and Trastuzumab Fixed-Dose Combination for Subcutaneous Administration (PH FDC SC) · Drug: Pertuzumab IV · Drug: Trastuzumab IV
In the Treatment Cross-Over Period of the study, participants randomized to Arm B first received the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) for 3 treatment cycles followed by pertuzumab intravenous (IV) and trastuzumab IV (P+H IV) administration for 3 treatment cycles (1 cycle = 21 days). Following completion of this study period, participants chose one of the two study treatments to receive in the Treatment Continuation Period for the remaining anti-HER2 treatment cycles (18 planned cycles in total, including pre-study neoadjuvant treatment). After completing study treatment, participants entered the Follow-up Period wherein they were to be followed for 3 years from the date the last participant was randomized.
Drug: Pertuzumab and Trastuzumab Fixed-Dose Combination for Subcutaneous Administration (PH FDC SC) · Drug: Pertuzumab IV · Drug: Trastuzumab IV
Drug page: Pertuzumab/Trastuzumab/Hyaluronidase-zzxf
PH FDC SC will be administered subcutaneously (SC) at a fixed non-weight-based dose. A loading dose of 1200 mg pertuzumab and 600 mg trastuzumab is then followed by a maintenance dose of 600 mg pertuzumab and 600 mg trastuzumab once every 3 weeks (Q3W).
Also known as: PH FDC SC, Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf, PHESGO™, RO7198574, RG6264
Pertuzumab will be administered intravenously (IV) as a fixed non-weight-based dose of 840-mg IV loading dose and then 420-mg IV maintenance dose Q3W.
Also known as: Perjeta®
Trastuzumab will be administered intravenously (IV) as an 8-mg/kg IV loading dose and then 6 mg/kg IV maintenance dose Q3W.
Also known as: Herceptin®
Percentage of Participants by Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 1 of the Patient Preference Questionnaire (PPQ)
Question 1 of the Patient Preference Questionnaire (PPQ) asked participants the following question: "All things considered, which method of administration did you prefer?" The three available options for a participant's response were: IV, SC, or No preference. A point estimate with associated exact Clopper-Pearson binomial 95% confidence interval was calculated only for the percentage of participants who preferred PH FDC SC.
Time frame: Cycle 6 Day 1 (each cycle is 21 days)
Percentage of Participants by Responses to the Strength of Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 2 of the Patient Preference Questionnaire (PPQ)
Question 1 of the Patient Preference Questionnaire (PPQ) was as follows: "All things considered, which method of administration did you prefer?" The available options for a participant's response were IV, SC, or No preference. In Question 2 of the PPQ, participants who reported a preference for one of the two administration routes in Question 1 of the PPQ were asked to rate the strength of their preference (very strong, fairly strong, not very strong).
Time frame: Cycle 6 Day 1 (each cycle is 21 days)
Percentage of Responses From Participants to the Two Main Reasons for Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 3 of the Patient Preference Questionnaire (PPQ)
In Question 3 of the PPQ, participants who reported a preference for one of the two administration routes in Question 1 of the PPQ were asked to provide the two main reasons for their preference. The five available options for a participant's response were: Feels less emotionally distressing; Requires less time in the clinic; Lower level of injection-site pain; Feels more comfortable during administration; and Other reason.
Time frame: Cycle 6 Day 1 (each cycle is 21 days)
Percentage of Participants by Their Level of Satisfaction With the Respective Methods of Administration (IV and SC), Question 1 of the Therapy Administration Satisfaction Questionnaire -Intravenous (TASQ-IV) and -Subcutaneous (TASQ-SC)
The Therapy Administration Satisfaction Questionnaire (TASQ) is a 12-item, patient-reported questionnaire measuring the impact of each mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on five domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. The TASQ-IV/-SC was administered at treatment Cycles 3 and 6 according to the order of treatment received per arm during the Cross-Over Period. Question 1 of the TASQ-IV/TASQ-SC is one of two items in the Satisfaction domain, with participants providing their answers to the following question: "How satisfied or dissatisfied were you with the IV infusion/SC injection?" The five available options for a participant's response were: very satisfied, satisfied, neither satisfied nor dissatisfied, dissatisfied, and very dissatisfied.
Time frame: Cycle 3 Day 1, Cycle 6 Day 1 (each cycle is 21 days)
Mean Scores of the Five Domains of the TASQ-IV and TASQ-SC (Satisfaction, Physical Impact, Psychological Impact, Impact on Activities of Daily Living, and Convenience) to Assess the Impact of IV and SC Routes of Administration
The TASQ is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains: Physical Impact (3 items: Question \[Q\]2. Pain, Q3. Swelling, Q4. Redness), Psychological Impact (1 item: Q5. Feeling restricted), Impact on Activities of Daily Living (1 item: Q8. Lost/gained time), Convenience (2 items: Q6. Is it convenient?, Q7. Bothered by the amount of time?), and Satisfaction (2 items: Q1. How satisfied or dissatisfied are you with treatment?, Q12: Would you recommend the way you received the treatment?). In addition, 3 questions in the TASQ (Q9, Q10, Q11) are not part of the domains. Responses for the 3 domains that contain more than 1 item were scored from 0 to 100, with a higher score indicating a better outcome. Responses for the 2 domains with 1 item were scored from 1 to 5, with a higher score indicating a better outcome.
Time frame: Cycle 3 Day 1, Cycle 6 Day 1 (each cycle is 21 days)
Percentage of Participants by Their Responses to Question 9 of the TASQ-IV and TASQ-SC, Assessing Whether Participants Receiving IV and SC Administration Have as Much Time as They Would Like to Talk to Their Nurse and/or Doctor About Their Illness
The TASQ is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains. In addition, 3 questions (Q.9-11) are not part of the domains. The TASQ-IV/-SC was administered at treatment Cycles 3 and 6 according to the order of treatment received per arm during the Cross-Over Period. Question 9 asked the participant, "When you receive the IV infusion/SC injection treatment, are you able to talk to your nurse and/or doctor as much as you would like about your illness?" There were five available response options: a) Yes, I had more than enough time to talk to my nurse and/or doctor; b) Yes, but I would have liked more time to talk to my nurse and/or doctor; c) It does not matter to me if I have time to talk to my nurse and/or doctor during my treatment; d) No, I did not have enough time to talk to my nurse and/or doctor; and e) No, I did not talk to my nurse and/or doctor at all.
Time frame: Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days)
Percentage of Participants by Their Responses to Question 10 of the TASQ-IV and TASQ-SC, Assessing Whether IV and SC Administration Have an Impact on the Amount of Time Participants Have to Talk to Their Nurse and/or Doctor About Their Illness
The Therapy Administration Satisfaction Questionnaire (TASQ) is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains (questions \[Q\] 1 to 8 and Q12): Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. In addition, 3 questions in the TASQ-IV/-SC (Q 9-11) are not part of the domains. The TASQ-IV/-SC were administered at treatment Cycles 3 and 6 according to the order of treatment received in each study arm during the Cross-Over Period. Question 10 of the TASQ-IV/-SC asked the participant "Does the IV infusion/SC injection impact the amount of time you have to talk to your nurse and/or doctor about your illness and other concerns?" There were two available options for the participant's response: Yes or No.
Time frame: Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days)
Percentage of Participants by Their Responses to Question 11 of the TASQ-IV and TASQ-SC, Assessing the Participants' Preferred Method for Receiving Cancer Treatment
The Therapy Administration Satisfaction Questionnaire (TASQ) is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains (questions \[Q\] 1 to 8 and Q12): Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. In addition, 3 questions in the TASQ-IV/-SC (Q 9-11) are not part of the domains. The TASQ-IV/-SC was administered at treatment Cycles 3 and 6 according to the order of treatment received during the Cross-Over Period. Question 11 of the TASQ-IV/-SC asked the participant, "There are two ways to get cancer treatment: a) IV infusion given through a port or small tube; b) SC (subcutaneous) injection in your thigh. Which would you prefer?" There were three available options for the participant's response: IV, SC, or No Preference.
Time frame: Cycle 3 Day 1 and Cycle 6 Day 1 (each cycle is 21 days)
Percentage of Participants by Their Choice of Treatment in the Treatment Continuation Period (PH FDC SC or P+H IV) and by Consistency of This Choice With Their Preferred Method of Administration Reported in Question 1 of the PPQ
At treatment Cycle 6, Day 1, participants were expected to select the study treatment formulation (PH FDC SC or P+H IV) they would receive during the Treatment Continuation Period (starting at Cycle 7) to complete their 18 cycles of neo/adjuvant HER2-targeted treatment. Additionally, for each participant's preference category (SC, IV, and No preference) as per the question 1 of the patient preference questionnaire (PPQ), the percentage of participants who selected each treatment administration route for the Treatment Continuation Period (PH FDC SC or P+H IV) was summarized.
Time frame: Cycle 6 Day 1 (each cycle is 21 days)
Duration of Treatment Administration Activities According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the Healthcare Professional Questionnaire (HCPQ) - Treatment Room
The Healthcare Professional Questionnaire (HCPQ)-Treatment Room Question 1 was completed at each treatment cycle of the Treatment Cross-Over Period by the healthcare professionals (HCPs) who administered treatment to the study's participants. HCPs responded to the following parts of Question 1 that sought to evaluate the amount of time it took to complete activities related to treatment administration: "If new IV access was needed for this cycle of treatment, please indicate what type of IV access was provided (central venous catheter, peripherally inserted central catheter, or peripheral vein cannulation) and how long (in minutes) this took to set up (only for participants receiving IV treatment)? How long (in minutes) did it take to administer the treatment, i.e. total infusion duration? How long (in minutes) was the patient in the Treatment Room for in total?"
Time frame: Day 1 of Cycles 1-6 (each cycle is 21 days)
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Treatment Room
HCPs who administered study treatment responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Treatment Room Question 2: "If all P+H IV infusions are switched to FDC SC injections, please indicate how strongly you agree or disagree with each of the following statements: a) Patients will be moved outside of infusion unit to receive FDC SC; b) FDC SC route will allow more flexible scheduling; c) More patients will be treated in the infusion unit; d) Waiting list for any P+H IV treatment at the infusion unit will be reduced; e) Staff resources will be redistributed to other departments of the hospital; f) There will still be sufficient interaction time between HCPs and patients; g) Staff will spend more time for further education/development; h) Staff will dedicate more time attending to administrative tasks for Perjeta-Herceptin patients; i) Patients will spend less time in the care unit; j) Administration by FDC SC injection is preferred by patients."
Time frame: Day 1 of Cycle 6 (each cycle is 21 days)
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use and Convenience of Each Study Regimen, Questions 3 to 7 of the HCPQ - Treatment Room
Healthcare professionals (HCPs) who administered study treatment responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Treatment Room Questions 3 to 7: "Looking back over the Perjeta-Herceptin treatment sessions, please indicate based on your opinion which administration method: Q3. Which Method Was Most Convenient for the Patient? Q4. Which Method Was Best for Optimizing Patient Care in Your Centre? Q5. Which Method Took the Least Time from Start to Finish of Administration? Q6. Which Method Required the Least Resource Use for Administration? Q7. Which Method Was Preferred by Patients?" The four available response options were: P+H IV, FDC SC, No Difference, and Unsure.
Time frame: Day 1 of Cycle 6 (each cycle is 21 days)
Percentage of Healthcare Professionals (HCPs) by Their Responses to Question 8 of the HCPQ - Treatment Room
Healthcare professionals (HCPs) who administered study treatment responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Treatment Room Question 8: "How frequently would you offer or recommend FDC SC administration to your patients in the future?" The three available response options were: Always, Sometimes, and Never.
Time frame: Day 1 of Cycle 6 (each cycle is 21 days)
Duration of Treatment Preparation According to Healthcare Professionals' Responses on Perception of Time by Treatment Cycle, Question 1 of the HCPQ - Drug Preparation Room
The Healthcare Professional Questionnaire (HCPQ)-Drug Preparation Room Question 1 was completed at each treatment cycle of the Treatment Cross-Over Period by the healthcare professionals (HCPs) within the pharmacy/drug preparation area where pertuzumab IV and trastuzumab IV and pertuzumab and trastuzumab FDC SC were prepared and dispensed for treating the study's participants. HCPs responded to the following question: "How long (in minutes) did it take to prepare the treatment for use?"
Time frame: Day 1 of Cycles 1-6 (each cycle is 21 days)
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Impact of PH FDC SC on Clinical Management and Clinical Efficiency, Question 2 of the HCPQ - Drug Preparation Room
Healthcare professionals (HCPs) who prepared study treatment within the pharmacy/drug preparation area responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Drug Preparation Room Question 2: "If all P+H IV infusions are switched to FDC SC injections, please indicate how strongly you agree or disagree with each of the following statements: a) Staff will have increased availability for other tasks in the pharmacy; b) Administrative procedures around FDC SC will require less time; c) FDC SC formulations will provide more flexibility for staff in managing their workload; d) Due to ready-to-use FDC SC formulations, potential dosing errors will be avoided; e) Due to ready-to-use FDC SC formulations, there will be less drug wastage; f) Without having to reconstitute the drug, less storage space for FDC SC related supplies will be required in the pharmacy; g) Preparation procedures and associated time staff time commitment will be reduced."
Time frame: Day 1 of Cycle 6 (each cycle is 21 days)
Percentage of Healthcare Professionals (HCPs) by Their Responses on Perception of Time/Resource Use of Each Study Regimen, Questions 3 and 4 of the HCPQ - Drug Preparation Room
Healthcare professionals (HCPs) who prepared study treatment within the pharmacy/drug preparation area responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Drug Preparation Room Questions 3 and 4: "Looking back over the Perjeta-Herceptin treatment sessions, please indicate based on your opinion which administration method: Q3. Was quickest from start to end of preparation to finish of administration (excluding observation period)?; Q4. Required less resource use for preparation and administration, for example nursing time, facility costs, equipment etc?" The three available response options were: P+H IV, FDC SC, and No Difference.
Time frame: Day 1 of Cycle 6 (each cycle is 21 days)
Change From Baseline Over Time in Health-Related Quality of Life (HRQoL) as Assessed by the Global Health Status (GHS)/HRQoL Scale Score of the the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30)
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Physical Functioning Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Role Functioning Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Emotional Functioning Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Cognitive Functioning Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Social Functioning Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Fatigue Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Nausea and Vomiting Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Pain Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Dyspnoea Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Insomnia Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Appetite Loss Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Constipation Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Diarrhoea Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Change From Baseline Over Time in the Financial Difficulties Scale Score of the EORTC QLQ-C30
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
Time frame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 3, 6, and 15 (or last treatment cycle; each cycle is 21 days); 1.5, 2, and 3 years (up to 3 years)
Safety Summary for Assessment of Switching Between the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over Period by Study Arm and Treatment Received
Investigators used the NCI CTCAE v4.0 grading scale for assessing adverse event (AE) severity; if not listed, AE severity was graded as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe or medically significant; Grade 4 = life-threatening; Grade 5 = death related to AE. Severity and seriousness are not synonymous and investigators independently assessed these criteria for each AE. Investigators also determined whether an AE was considered to be related to the study drug. Adverse events to monitor were defined based on known risks associated with the study drugs and included: hypersensitivity reactions, administration-related reactions (ARRs), cardiac dysfunction, diarrhea grade ≥3, rash/skin reactions, mucositis, interstitial lung disease (ILD), (febrile) neutropenia, pulmonary events that may occur as a result of an ARR, and pregnancy/neonatal related. Multiple occurrences of AEs were counted only once per participant. LVEF = left ventricular ejection fraction
Time frame: From Day 1 of Cycle 1 to the end of Cycle 3 of Cross-Over Period; from Day 1 of Cycle 4 to the end of Cycle 6 of Cross-Over Period (1 cycle is 21 days)
Safety Summary of the FDC SC and IV Formulations: Number of Participants With at Least One Adverse Event During the Treatment Cross-Over and Treatment Continuation Periods
Investigators used the NCI CTCAE v4.0 grading scale for assessing adverse event (AE) severity; if not listed, AE severity was graded as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe or medically significant; Grade 4 = life-threatening; Grade 5 = death related to AE. Severity and seriousness are not synonymous and investigators independently assessed these criteria for each AE. Investigators also determined whether an AE was considered to be related to the study drug. Adverse events to monitor were defined based on known risks associated with the study drugs and included: hypersensitivity reactions, administration-related reactions (ARRs), cardiac dysfunction, diarrhea grade ≥3, rash/skin reactions, mucositis, interstitial lung disease (ILD), (febrile) neutropenia, pulmonary events that may occur as a result of an ARR, and pregnancy/neonatal related. Multiple occurrences of AEs were counted only once per participant. LVEF = left ventricular ejection fraction
Time frame: From Day 1 of Cycle 1 to end of Cycle 6 of the Treatment Cross-Over Period; from Day 1 of Cycle 7 up to the completion of 18 cycles of neo/adjuvant anti-HER2 treatment in the Treatment Continuation Period (1 cycle is 21 days)
Number of Participants With at Least One Event of Heart Failure With the FDC SC and IV Formulations During the Treatment Cross-Over and Treatment Continuation Periods
Heart failure is defined as a disorder characterized by the inability of the heart to pump blood at an adequate volume to meet tissue metabolic requirements, or, the ability to do only at an elevation in the filling pressure. Any adverse event of symptomatic left ventricular systolic dysfunction (LVSD; also referred to as heart failure) occurring during the study was to be reported as a serious adverse event.
Time frame: From Day 1 of Cycle 1 to end of Cycle 6 of the Treatment Cross-Over Period; from Day 1 of Cycle 7 up to the completion of 18 cycles of neo/adjuvant anti-HER2 treatment in the Treatment Continuation Period (1 cycle is 21 days)
Number of Participants With at Least One Event of Ejection Fraction Decreased With the FDC SC and IV Formulations During the Treatment Cross-Over and Treatment Continuation Periods
Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. All participants who enrolled in this study must have had a baseline LVEF ≥55%. Verbatim description of adverse events was mapped to Medical Dictionary for Regulatory Activities (MedDRA) version 25.1. The MedDRA preferred term of 'ejection fraction decreased' is defined as an LVEF decrease of at least 10 percentage points from baseline and to below 50%.
Time frame: Baseline; Day 1 of Cycles 4, 7, and 11 (each cycle is 21 days); End of Treatment Visit (up to 1 year)
Number of Participants With Targeted Vital Signs Outside the Normal Limits Among Those Without an Abnormality at Baseline During the Treatment Cross-Over and Treatment Continuation Periods
The number of participants at any post-baseline timepoint with abnormal readings outside the normal range for vital signs of diastolic and systolic blood pressure, pulse rate, respiratory rate, and body temperature were summarized according the specified direction of the abnormal reading (high or low). The number analyzed (denominator) in the results table represents participants without the specified abnormal vital sign at baseline. Not every vital sign abnormality qualified as an adverse event (AE). A vital sign result must have been reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption, or treatment discontinuation); resulted in a medical intervention or a change in concomitant therapy; or, was clinically significant in the investigator's judgment.
Time frame: Pre-dose at Day 1 of Cycles 1 (baseline), 4, and 7, and end of treatment (up to 18 cycles; 1 cycle is 21 days)
Number of Participants With Chemistry and Hematology Laboratory Test Result Shifts From NCI-CTCAE Grade 0-2 at Baseline to Grade 3-4 Post-Baseline During the Treatment Cross-Over and Treatment Continuation Periods
Laboratory data for targeted chemistry and hematology parameters were classified according to the NCI CTCAE v4.0; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). The results show the shifts in the number of participants with Grade 0-2 at baseline to Grade 3-4 post-baseline; those with missing baseline values were counted as Grade 0-2 at baseline. Not every laboratory abnormality qualified as an adverse event, only if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption, or treatment discontinuation); resulted in a medical intervention or a change in concomitant therapy; or, was clinically significant in the investigator's judgment. SGOT/AST = aspartate aminotransferase; SGPT/ALT = alanine aminotransferase
Time frame: Pre-dose at Day 1 of Cycles 1 (baseline), 4, 7, 11, 15, and end of treatment (up to 18 cycles; 1 cycle is 21 days)
Number of Participants With an Event for Overall Survival, Overall and by Treatment Sequence
Overall survival (OS) is defined as the time from randomization to death due to any cause. The number of participants who had an OS event (i.e., died) while on study is reported.
Time frame: Up to 3 years, 10 months
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Overall Survival, Overall and by Treatment Sequence
Overall survival is defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization +1 day. Kaplan-Meier methodology was used to estimate the percentage of participants who were alive (event-free) at 12, 24, and 36 months.
Time frame: At 12, 24, and 36 months
Number of Participants With an Event for Invasive Disease-Free Survival Including Second Primary Non-Breast Cancer, Overall and by Treatment Sequence
Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Second primary non-breast invasive cancer (with the exception of non-melanoma skin cancers and in situ carcinoma of any site) was included as an event.
Time frame: Up to 3 years, 10 months
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Invasive Disease-Free Survival Including Second Primary Non-Breast Cancer, Overall and by Treatment Sequence
Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Second primary non-breast invasive cancer (with the exception of non-melanoma skin cancers and in situ carcinoma of any site) was included as an event. Participants who had not experienced invasive disease at the time of analysis were censored: i) at the time of the last clinical breast examination if they had post-baseline clinical breast examination; ii) on the date of randomization +1 day if no post-baseline clinical breast examination. Kaplan-Meier methodology was used to estimate the percentage of participants who were event-free at 12, 24, and 36 months.
Time frame: At 12, 24, and 36 months
Number of Participants With an Event for Invasive Disease-Free Survival, Overall and by Treatment Sequence
Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) were not counted as recurrence.
Time frame: Up to 3 years, 10 months
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Invasive Disease-Free Survival, Overall and by Treatment Sequence
Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) were not counted as recurrence. Participants who had not experienced invasive disease at the time of analysis were censored: i) at the time of the last clinical breast examination if they had post-baseline clinical breast examination; ii) on the date of randomization +1 day if no post-baseline clinical breast examination. Kaplan-Meier methodology was used to estimate the percentage of participants who were event-free at 12, 24, and 36 months.
Time frame: At 12, 24, and 36 months
Number of Participants With an Event for Distant Disease-Free Survival, Overall and by Treatment Sequence
Distant disease-free survival (DDFS) is defined as the time from randomization to the date of distant breast cancer recurrence (i.e., evidence of breast cancer in any anatomic site other than for ipsilateral \[loco-regional\] invasive breast cancer recurrence that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer).
Time frame: Up to 3 years, 10 months
Kaplan-Meier Estimate of the Percentage of Participants Who Were Event-Free for Distant Disease-Free Survival, Overall and by Treatment Sequence
Distant disease-free survival (DDFS) is defined as the time from randomization to the date of distant breast cancer recurrence (i.e., evidence of breast cancer in any anatomic site other than for ipsilateral \[loco-regional\] invasive breast cancer recurrence that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer). Participants who had not experienced invasive disease at the time of analysis were censored: i) at the time of the last clinical breast examination if they had post-baseline clinical breast examination; ii) on the date of randomization +1 day if no post-baseline clinical breast examination. Kaplan-Meier methodology was used to estimate the percentage of participants who were event-free at 12, 24, and 36 months.
Time frame: At 12, 24, and 36 months
A total of 183 patients were screened and 160 participants were enrolled.
| Milestone | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|
| Started | 80 | 80 |
| Completed cross-over treatment | 80 | 80 |
| Completed | 79 | 80 |
| Not completed | 1 | 0 |
| Withdrew: Adverse event | 1 | 0 |
| Milestone | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|
| Started | 79 | 80 |
| Received ph fdc sc for treatment continuation | 70 | 68 |
| Received p+h iv for treatment continuation | 9 | 12 |
| Completed continuation treatment | 78 | 77 |
| Completed | 78 | 77 |
| Not completed | 1 | 3 |
| Withdrew: Reason not specified | 0 | 2 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Withdrew: Disease relapse | 1 | 0 |
| Milestone | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|
| Started | 80 | 79 |
| Completed | 73 | 75 |
| Not completed | 7 | 4 |
| Withdrew: Withdrawal by subject | 2 | 2 |
| Withdrew: Lost to follow-up | 2 | 1 |
| Withdrew: Death | 2 | 0 |
| Withdrew: Reason not specified | 1 | 1 |
Question 1 of the Patient Preference Questionnaire (PPQ) asked participants the following question: "All things considered, which method of administration did you prefer?" The three available options for a participant's response were: IV, SC, or No preference. A point estimate with associated exact Clopper-Pearson binomial 95% confidence interval was calculated only for the percentage of participants who preferred PH FDC SC.
| Percentage of participants | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| SC Preference | 85.00 (78.51 to 90.15) | 87.50 (78.21 to 93.84) | 82.50 (72.38 to 90.09) |
| IV Preference | 13.8 (NA to NA) | 12.5 (NA to NA) | 15.0 (NA to NA) |
| No Preference | 1.3 (NA to NA) | 0.0 (NA to NA) | 2.5 (NA to NA) |
Question 1 of the Patient Preference Questionnaire (PPQ) was as follows: "All things considered, which method of administration did you prefer?" The available options for a participant's response were IV, SC, or No preference. In Question 2 of the PPQ, participants who reported a preference for one of the two administration routes in Question 1 of the PPQ were asked to rate the strength of their preference (very strong, fairly strong, not very strong).
| Percentage of participants | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| SC Preference: Very Strong | 67.6 | 68.6 | 66.7 |
| SC Preference: Fairly Strong | 25.0 | 24.3 | 25.8 |
| SC Preference: Not Very Strong | 7.4 | 7.1 | 7.6 |
| IV Preference: Very Strong | 54.5 | 40.0 | 66.7 |
| IV Preference: Fairly Strong | 9.1 | 10.0 | 8.3 |
| IV Preference: Not Very Strong | 36.4 | 50.0 | 25.0 |
In Question 3 of the PPQ, participants who reported a preference for one of the two administration routes in Question 1 of the PPQ were asked to provide the two main reasons for their preference. The five available options for a participant's response were: Feels less emotionally distressing; Requires less time in the clinic; Lower level of injection-site pain; Feels more comfortable during administration; and Other reason.
| Percentage of responses | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| SC Preference: Feels Less Emotionally Distressing | 16.3 | 14.7 | 18.0 |
| SC Preference: Requires Less Time in the Clinic | 42.2 | 42.0 | 42.4 |
| SC Preference: Lower Level of Injection-Site Pain | 11.3 | 9.8 | 12.9 |
| SC Preference: Feels More Comfortable During Administration | 25.9 | 28.7 | 23.0 |
| SC Preference: Other Reason | 4.3 | 4.9 | 3.6 |
| IV Preference: Feels Less Emotionally Distressing | 16.7 | 17.6 | 16.0 |
| IV Preference: Requires Less Time in the Clinic | 4.8 | 5.9 | 4.0 |
| IV Preference: Lower Level of Injection-Site Pain | 26.2 | 23.5 | 28.0 |
| IV Preference: Feels More Comfortable During Administration | 33.3 | 47.1 | 24.0 |
| IV Preference: Other Reason | 19.0 | 5.9 | 28.0 |
The Therapy Administration Satisfaction Questionnaire (TASQ) is a 12-item, patient-reported questionnaire measuring the impact of each mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on five domains: Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. The TASQ-IV/-SC was administered at treatment Cycles 3 and 6 according to the order of treatment received per arm during the Cross-Over Period. Question 1 of the TASQ-IV/TASQ-SC is one of two items in the Satisfaction domain, with participants providing their answers to the following question: "How satisfied or dissatisfied were you with the IV infusion/SC injection?" The five available options for a participant's response were: very satisfied, satisfied, neither satisfied nor dissatisfied, dissatisfied, and very dissatisfied.
| Percentage of participants | All Participants: TASQ-IV Completers | All Participants: TASQ-SC Completers |
|---|---|---|
| Very Satisfied | 25.6 | 57.5 |
| Satisfied | 41.9 | 30.6 |
| Neither Satisfied nor Dissatisfied | 25.6 | 4.4 |
| Dissatisfied | 5.6 | 1.9 |
| Very Dissatisfied | 1.3 | 4.4 |
| Did Not Answer Question | 0.0 | 1.3 |
The TASQ is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains: Physical Impact (3 items: Question \[Q\]2. Pain, Q3. Swelling, Q4. Redness), Psychological Impact (1 item: Q5. Feeling restricted), Impact on Activities of Daily Living (1 item: Q8. Lost/gained time), Convenience (2 items: Q6. Is it convenient?, Q7. Bothered by the amount of time?), and Satisfaction (2 items: Q1. How satisfied or dissatisfied are you with treatment?, Q12: Would you recommend the way you received the treatment?). In addition, 3 questions in the TASQ (Q9, Q10, Q11) are not part of the domains. Responses for the 3 domains that contain more than 1 item were scored from 0 to 100, with a higher score indicating a better outcome. Responses for the 2 domains with 1 item were scored from 1 to 5, with a higher score indicating a better outcome.
| Score on a scale | All Participants: TASQ-IV Completers | All Participants: TASQ-SC Completers |
|---|---|---|
| Satisfaction Domain | 64.3 ± 23.6 | 87.7 ± 17.5 |
| Physical Impact Domain | 86.5 ± 14.8 | 81.3 ± 15.4 |
| Psychological Impact Domain | 3.8 ± 1.2 | 4.6 ± 0.7 |
| Impact on Activities of Daily Living Domain | 2.3 ± 0.9 | 3.9 ± 1.0 |
| Convenience Domain | 56.8 ± 26.0 | 90.0 ± 13.8 |
The TASQ is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains. In addition, 3 questions (Q.9-11) are not part of the domains. The TASQ-IV/-SC was administered at treatment Cycles 3 and 6 according to the order of treatment received per arm during the Cross-Over Period. Question 9 asked the participant, "When you receive the IV infusion/SC injection treatment, are you able to talk to your nurse and/or doctor as much as you would like about your illness?" There were five available response options: a) Yes, I had more than enough time to talk to my nurse and/or doctor; b) Yes, but I would have liked more time to talk to my nurse and/or doctor; c) It does not matter to me if I have time to talk to my nurse and/or doctor during my treatment; d) No, I did not have enough time to talk to my nurse and/or doctor; and e) No, I did not talk to my nurse and/or doctor at all.
| Percentage of participants | All Participants: TASQ-IV Completers | All Participants: TASQ-SC Completers |
|---|---|---|
| a) Yes, I had enough time to talk to my nurse and/or doctor | 82.5 | 90.0 |
| b) Yes, but I would have liked more time to talk to my nurse and/or doctor | 9.4 | 5.0 |
| c) It does not matter to me if I have time to talk to my nurse and/or doctor | 5.0 | 3.1 |
| d) No, I did not have enough time to talk to my nurse and/or doctor | 0.6 | 0.6 |
| e) No, I did not talk to my nurse and/or doctor at all | 2.5 | 0.0 |
| Patient did not answer question | 0.0 | 1.3 |
The Therapy Administration Satisfaction Questionnaire (TASQ) is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains (questions \[Q\] 1 to 8 and Q12): Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. In addition, 3 questions in the TASQ-IV/-SC (Q 9-11) are not part of the domains. The TASQ-IV/-SC were administered at treatment Cycles 3 and 6 according to the order of treatment received in each study arm during the Cross-Over Period. Question 10 of the TASQ-IV/-SC asked the participant "Does the IV infusion/SC injection impact the amount of time you have to talk to your nurse and/or doctor about your illness and other concerns?" There were two available options for the participant's response: Yes or No.
| Percentage of participants | All Participants: TASQ-IV Completers | All Participants: TASQ-SC Completers |
|---|---|---|
| Yes | 20.0 | 13.1 |
| No | 79.4 | 85.0 |
| Patient Did Not Answer Question | 0.6 | 1.9 |
The Therapy Administration Satisfaction Questionnaire (TASQ) is a 12-item, patient-reported questionnaire measuring the impact of the mode of treatment administration (TASQ-IV for IV treatment and TASQ-SC for SC treatment) on 5 domains (questions \[Q\] 1 to 8 and Q12): Physical Impact, Psychological Impact, Impact on Activities of Daily Living, Convenience, and Satisfaction. In addition, 3 questions in the TASQ-IV/-SC (Q 9-11) are not part of the domains. The TASQ-IV/-SC was administered at treatment Cycles 3 and 6 according to the order of treatment received during the Cross-Over Period. Question 11 of the TASQ-IV/-SC asked the participant, "There are two ways to get cancer treatment: a) IV infusion given through a port or small tube; b) SC (subcutaneous) injection in your thigh. Which would you prefer?" There were three available options for the participant's response: IV, SC, or No Preference.
| Percentage of participants | All Participants: TASQ-IV Completers | All Participants: TASQ-SC Completers |
|---|---|---|
| Prefer IV Method | 11.9 | 9.4 |
| Prefer SC Method | 70.6 | 82.5 |
| No Preference | 11.9 | 5.6 |
| Patient Did Not Answer Question | 5.6 | 2.5 |
At treatment Cycle 6, Day 1, participants were expected to select the study treatment formulation (PH FDC SC or P+H IV) they would receive during the Treatment Continuation Period (starting at Cycle 7) to complete their 18 cycles of neo/adjuvant HER2-targeted treatment. Additionally, for each participant's preference category (SC, IV, and No preference) as per the question 1 of the patient preference questionnaire (PPQ), the percentage of participants who selected each treatment administration route for the Treatment Continuation Period (PH FDC SC or P+H IV) was summarized.
| Percentage of participants | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Chose PH FDC SC for Treatment Continuation | 86.9 | 88.8 | 85.0 |
| Chose P+H IV for Treatment Continuation | 13.1 | 11.3 | 15.0 |
| Preferred SC per the PPQ and Chose PH FDC SC for Continuation | 85.0 | 87.5 | 82.5 |
| Preferred SC per the PPQ and Chose P+H IV for Continuation | 0.0 | 0.0 | 0.0 |
| Preferred IV per the PPQ and Chose PH FDC SC for Continuation | 0.6 | 1.3 | 0.0 |
| Preferred IV per the PPQ and Chose P+H IV for Continuation | 13.1 | 11.3 | 15.0 |
| No Preference per the PPQ and Chose PH FDC SC for Continuation | 1.3 | 0.0 | 2.5 |
| No Preference per the PPQ and Chose P+H IV for Continuation | 0.0 | 0.0 | 0.0 |
The Healthcare Professional Questionnaire (HCPQ)-Treatment Room Question 1 was completed at each treatment cycle of the Treatment Cross-Over Period by the healthcare professionals (HCPs) who administered treatment to the study's participants. HCPs responded to the following parts of Question 1 that sought to evaluate the amount of time it took to complete activities related to treatment administration: "If new IV access was needed for this cycle of treatment, please indicate what type of IV access was provided (central venous catheter, peripherally inserted central catheter, or peripheral vein cannulation) and how long (in minutes) this took to set up (only for participants receiving IV treatment)? How long (in minutes) did it take to administer the treatment, i.e. total infusion duration? How long (in minutes) was the patient in the Treatment Room for in total?"
| minutes | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|
| Cycle 1. Duration of Central Venous Catheter Set Up (IV Only)? | 5.0 (4 to 6) | — |
| Cycle 1. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)? | 5.0 (5 to 5) | — |
| Cycle 1. Duration of Peripheral Vein Cannulation Set Up (IV Only)? | 5.0 (1 to 40) | — |
| Cycle 1. How Long Did it Take to Administer the Treatment? | 150.0 (60 to 396) | 8.0 (2 to 17) |
| Cycle 1. How Long Was the Patient in the Treatment Room in Total? | 300.0 (90 to 450) | 50.0 (8 to 240) |
| Cycle 2. Duration of Central Venous Catheter Set Up (IV Only)? | 5.0 (3 to 5) | — |
| Cycle 2. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)? | 3.0 (3 to 3) | — |
| Cycle 2. Duration of Peripheral Vein Cannulation Set Up (IV Only)? | 5.0 (1 to 20) | — |
| Cycle 2. How Long Did it Take to Administer the Treatment? | 90.0 (8 to 260) | 8.0 (5 to 20) |
| Cycle 2. How Long Was the Patient in the Treatment Room in Total? | 153.0 (30 to 342) | 40.0 (8 to 225) |
| Cycle 3. Duration of Central Venous Catheter Set Up (IV Only)? | 5.0 (3 to 10) | — |
| Cycle 3. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)? | 3.0 (3 to 3) | — |
| Cycle 3. Duration of Peripheral Vein Cannulation Set Up (IV Only)? | 5.0 (1 to 30) | — |
| Cycle 3. How Long Did it Take to Administer the Treatment? | 70.0 (30 to 240) | 7.5 (4 to 16) |
| Cycle 3. How Long Was the Patient in the Treatment Room in Total? | 150.0 (105 to 330) | 36.0 (5 to 327) |
| Cycle 4. Duration of Central Venous Catheter Set Up (IV Only)? | — | 5.0 (2 to 10) |
| Cycle 4. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)? | — | 42.0 (42 to 42) |
| Cycle 4. Duration of Peripheral Vein Cannulation Set Up (IV Only)? | — | 5.0 (1 to 20) |
| Cycle 4. How Long Did it Take to Administer the Treatment? | 8.0 (4 to 12) | 60.0 (30 to 210) |
| Cycle 4. How Long Was the Patient in the Treatment Room in Total? | 45.0 (1 to 185) | 150.0 (80 to 480) |
| Cycle 5. Duration of Central Venous Catheter Set Up (IV Only)? | — | 3.0 (2 to 10) |
| Cycle 5. Duration of Peripherally Inserted Central Catheter Set Up (IV Only)? | — | 10.0 (10 to 10) |
| Cycle 5. Duration of Peripheral Vein Cannulation Set Up (IV Only)? | — | 5.0 (1 to 20) |
| Cycle 5. How Long Did it Take to Administer the Treatment? | 8.0 (3 to 14) | 83.0 (30 to 200) |
| Cycle 5. How Long Was the Patient in the Treatment Room in Total? | 33.0 (8 to 135) | 150.0 (95 to 343) |
| Cycle 6. Duration of Central Venous Catheter Set Up (IV Only)? | — | 10.0 (1 to 91) |
| Cycle 6. Duration of Peripheral Vein Cannulation Set Up (IV Only)? | — | 5.0 (1 to 60) |
| Cycle 6. How Long Did it Take to Administer the Treatment? | 7.0 (3 to 11) | 60.0 (5 to 275) |
| Cycle 6. How Long Was the Patient in the Treatment Room in Total? | 35.0 (10 to 150) | 130.0 (45 to 330) |
HCPs who administered study treatment responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Treatment Room Question 2: "If all P+H IV infusions are switched to FDC SC injections, please indicate how strongly you agree or disagree with each of the following statements: a) Patients will be moved outside of infusion unit to receive FDC SC; b) FDC SC route will allow more flexible scheduling; c) More patients will be treated in the infusion unit; d) Waiting list for any P+H IV treatment at the infusion unit will be reduced; e) Staff resources will be redistributed to other departments of the hospital; f) There will still be sufficient interaction time between HCPs and patients; g) Staff will spend more time for further education/development; h) Staff will dedicate more time attending to administrative tasks for Perjeta-Herceptin patients; i) Patients will spend less time in the care unit; j) Administration by FDC SC injection is preferred by patients."
| Percentage of HCPs | All Healthcare Professionals | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Statement a): Strongly Disagree | 16.4 | 11.4 | 21.3 |
| Statement a): Disagree | 15.1 | 12.7 | 17.5 |
| Statement a): Neutral | 6.3 | 8.9 | 3.8 |
| Statement a): Agree | 21.4 | 26.6 | 16.3 |
| Statement a): Strongly Agree | 22.6 | 22.8 | 22.5 |
| Statement a): Not Applicable | 12.6 | 13.9 | 11.3 |
| Statement a): Answer Missing | 5.7 | 3.8 | 7.5 |
| Statement b): Strongly Disagree | 3.1 | 0.0 | 6.3 |
| Statement b): Disagree | 8.8 | 7.6 | 10.0 |
| Statement b): Neutral | 8.8 | 10.1 | 7.5 |
| Statement b): Agree | 28.3 | 29.1 | 27.5 |
| Statement b): Strongly Agree | 45.3 | 49.4 | 41.3 |
| Statement b): Not Applicable | 0.0 | 0.0 | 0.0 |
| Statement b): Answer Missing | 5.7 | 3.8 | 7.5 |
| Statement c): Strongly Disagree | 2.5 | 1.3 | 3.8 |
| Statement c): Disagree | 7.5 | 7.6 | 7.5 |
| Statement c): Neutral | 15.1 | 17.7 | 12.5 |
| Statement c): Agree | 30.2 | 29.1 | 31.3 |
| Statement c): Strongly Agree | 37.1 | 36.7 | 37.5 |
| Statement c): Not Applicable | 1.9 | 3.8 | 0.0 |
| Statement c): Answer Missing | 5.7 | 3.8 | 7.5 |
| Statement d): Strongly Disagree | 4.4 | 1.3 | 7.5 |
| Statement d): Disagree | 8.2 | 8.9 | 7.5 |
| Statement d): Neutral | 14.5 | 17.7 | 11.3 |
| Statement d): Agree | 27.7 | 29.1 | 26.3 |
| Statement d): Strongly Agree | 35.2 | 36.7 | 33.8 |
| Statement d): Not Applicable | 3.8 | 2.5 | 5.0 |
| Statement d): Answer Missing | 6.3 | 3.8 | 8.8 |
| Statement e): Strongly Disagree | 12.6 | 15.2 | 10.0 |
| Statement e): Disagree | 19.5 | 16.5 | 22.5 |
| Statement e): Neutral | 20.1 | 17.7 | 22.5 |
| Statement e): Agree | 15.1 | 19.0 | 11.3 |
| Statement e): Strongly Agree | 19.5 | 20.3 | 18.8 |
| Statement e): Not Applicable | 6.9 | 7.6 | 6.3 |
| Statement e): Answer Missing | 6.3 | 3.8 | 8.8 |
| Statement f): Strongly Disagree | 1.9 | 0.0 | 3.8 |
| Statement f): Disagree | 5.0 | 6.3 | 3.8 |
| Statement f): Neutral | 15.7 | 15.2 | 16.3 |
| Statement f): Agree | 32.1 | 31.6 | 32.5 |
| Statement f): Strongly Agree | 39.0 | 43.0 | 35.0 |
| Statement f): Not Applicable | 0.0 | 0.0 | 0.0 |
| Statement f): Answer Missing | 6.3 | 3.8 | 8.8 |
| Statement g): Strongly Disagree | 2.5 | 0.0 | 5.0 |
| Statement g): Disagree | 9.4 | 7.6 | 11.3 |
| Statement g): Neutral | 27.7 | 31.6 | 23.8 |
| Statement g): Agree | 21.4 | 20.3 | 22.5 |
| Statement g): Strongly Agree | 31.4 | 35.4 | 27.5 |
| Statement g): Not Applicable | 1.9 | 1.3 | 2.5 |
| Statement g): Answer Missing | 5.7 | 3.8 | 7.5 |
| Statement h): Strongly Disagree | 3.1 | 1.3 | 5.0 |
| Statement h): Disagree | 13.8 | 11.4 | 16.3 |
| Statement h): Neutral | 24.5 | 25.3 | 23.8 |
| Statement h): Agree | 20.1 | 24.1 | 16.3 |
| Statement h): Strongly Agree | 30.2 | 32.9 | 27.5 |
| Statement h): Not Applicable | 2.5 | 1.3 | 3.8 |
| Statement h): Answer Missing | 5.7 | 3.8 | 7.5 |
| Statement i): Strongly Disagree | 0.0 | 0.0 | 0.0 |
| Statement i): Disagree | 5.0 | 6.3 | 3.8 |
| Statement i): Neutral | 3.1 | 1.3 | 5.0 |
| Statement i): Agree | 25.2 | 27.8 | 22.5 |
| Statement i): Strongly Agree | 60.4 | 60.8 | 60.0 |
| Statement i): Not Applicable | 0.0 | 0.0 | 0.0 |
| Statement i): Answer Missing | 6.3 | 3.8 | 8.8 |
| Statement j): Strongly Disagree | 0.0 | 0.0 | 0.0 |
| Statement j): Disagree | 5.0 | 8.9 | 1.3 |
| Statement j): Neutral | 12.6 | 10.1 | 15.0 |
| Statement j): Agree | 24.5 | 22.8 | 26.3 |
| Statement j): Strongly Agree | 50.3 | 53.2 | 47.5 |
| Statement j): Not Applicable | 1.3 | 1.3 | 1.3 |
| Statement j): Answer Missing | 6.3 | 3.8 | 8.8 |
Healthcare professionals (HCPs) who administered study treatment responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Treatment Room Questions 3 to 7: "Looking back over the Perjeta-Herceptin treatment sessions, please indicate based on your opinion which administration method: Q3. Which Method Was Most Convenient for the Patient? Q4. Which Method Was Best for Optimizing Patient Care in Your Centre? Q5. Which Method Took the Least Time from Start to Finish of Administration? Q6. Which Method Required the Least Resource Use for Administration? Q7. Which Method Was Preferred by Patients?" The four available response options were: P+H IV, FDC SC, No Difference, and Unsure.
| Percentage of HCPs | All Healthcare Professionals | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Q3. Answer: FDC SC | 86.8 | 88.6 | 85.0 |
| Q3. Answer: P+H IV | 3.8 | 6.3 | 1.3 |
| Q3. Answer: No Difference | 3.8 | 2.5 | 5.0 |
| Q3. Answer: Unsure | 3.8 | 0.0 | 7.5 |
| Q3. Answer: Missing | 1.9 | 2.5 | 1.3 |
| Q4. Answer: FDC SC | 79.2 | 79.7 | 78.8 |
| Q4. Answer: P+H IV | 2.5 | 3.8 | 1.3 |
| Q4. Answer: No Difference | 12.6 | 12.7 | 12.5 |
| Q4. Answer: Unsure | 3.8 | 1.3 | 6.3 |
| Q4. Answer: Missing | 1.9 | 2.5 | 1.3 |
| Q5. Answer: FDC SC | 95.6 | 94.9 | 96.3 |
| Q5. Answer: P+H IV | 0.0 | 0.0 | 0.0 |
| Q5. Answer: No Difference | 2.5 | 2.5 | 2.5 |
| Q5. Answer: Unsure | 0.0 | 0.0 | 0.0 |
| Q5. Answer: Missing | 1.9 | 2.5 | 1.3 |
| Q6. Answer: FDC SC | 86.2 | 83.5 | 88.8 |
| Q6. Answer: P+H IV | 0.6 | 0.0 | 1.3 |
| Q6. Answer: No Difference | 11.3 | 13.9 | 8.8 |
| Q6. Answer: Unsure | 0.0 | 0.0 | 0.0 |
| Q6. Answer: Missing | 1.9 | 2.5 | 1.3 |
| Q7. Answer: FDC SC | 77.4 | 77.2 | 77.5 |
| Q7. Answer: P+H IV | 6.3 | 7.6 | 5.0 |
| Q7. Answer: No Difference | 2.5 | 2.5 | 2.5 |
| Q7. Answer: Unsure | 11.9 | 10.1 | 13.8 |
| Q7. Answer: Missing | 1.9 | 2.5 | 1.3 |
Healthcare professionals (HCPs) who administered study treatment responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Treatment Room Question 8: "How frequently would you offer or recommend FDC SC administration to your patients in the future?" The three available response options were: Always, Sometimes, and Never.
| Percentage of HCPs | All Healthcare Professionals | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Always | 67.3 | 69.6 | 65.0 |
| Sometimes | 30.2 | 26.6 | 33.8 |
| Never | 0.6 | 1.3 | 0.0 |
| Missing | 1.9 | 2.5 | 1.3 |
The Healthcare Professional Questionnaire (HCPQ)-Drug Preparation Room Question 1 was completed at each treatment cycle of the Treatment Cross-Over Period by the healthcare professionals (HCPs) within the pharmacy/drug preparation area where pertuzumab IV and trastuzumab IV and pertuzumab and trastuzumab FDC SC were prepared and dispensed for treating the study's participants. HCPs responded to the following question: "How long (in minutes) did it take to prepare the treatment for use?"
| minutes | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|
| Cycle 1 | 20.0 (3 to 60) | 5.0 (1 to 50) |
| Cycle 2 | 20.0 (3 to 60) | 5.0 (1 to 30) |
| Cycle 3 | 17.5 (3 to 90) | 5.0 (1 to 40) |
| Cycle 4 | 5.0 (1 to 30) | 15.0 (3 to 49) |
| Cycle 5 | 5.0 (1 to 35) | 15.0 (3 to 50) |
| Cycle 6 | 5.0 (1 to 40) | 15.0 (3 to 50) |
Healthcare professionals (HCPs) who prepared study treatment within the pharmacy/drug preparation area responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Drug Preparation Room Question 2: "If all P+H IV infusions are switched to FDC SC injections, please indicate how strongly you agree or disagree with each of the following statements: a) Staff will have increased availability for other tasks in the pharmacy; b) Administrative procedures around FDC SC will require less time; c) FDC SC formulations will provide more flexibility for staff in managing their workload; d) Due to ready-to-use FDC SC formulations, potential dosing errors will be avoided; e) Due to ready-to-use FDC SC formulations, there will be less drug wastage; f) Without having to reconstitute the drug, less storage space for FDC SC related supplies will be required in the pharmacy; g) Preparation procedures and associated time staff time commitment will be reduced."
| Percentage of HCPs | All Healthcare Professionals | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Statement a): Strongly Disagree | 1.3 | 1.3 | 1.3 |
| Statement a): Disagree | 0.6 | 1.3 | 0.0 |
| Statement a): Neutral | 7.5 | 8.8 | 6.3 |
| Statement a): Agree | 28.8 | 28.8 | 28.8 |
| Statement a): Strongly Agree | 50.6 | 52.5 | 48.8 |
| Statement a): Not Applicable | 2.5 | 3.8 | 1.3 |
| Statement a): Answer Missing | 8.8 | 3.8 | 13.8 |
| Statement b): Strongly Disagree | 5.6 | 8.8 | 2.5 |
| Statement b): Disagree | 3.8 | 3.8 | 3.8 |
| Statement b): Neutral | 14.4 | 16.3 | 12.5 |
| Statement b): Agree | 18.1 | 17.5 | 18.8 |
| Statement b): Strongly Agree | 46.3 | 46.3 | 46.3 |
| Statement b): Not Applicable | 2.5 | 2.5 | 2.5 |
| Statement b): Answer Missing | 9.4 | 5.0 | 13.8 |
| Statement c): Strongly Disagree | 0.6 | 0.0 | 1.3 |
| Statement c): Disagree | 0.6 | 0.0 | 1.3 |
| Statement c): Neutral | 13.1 | 15.0 | 11.3 |
| Statement c): Agree | 26.3 | 28.8 | 23.8 |
| Statement c): Strongly Agree | 48.8 | 50.0 | 47.5 |
| Statement c): Not Applicable | 1.3 | 1.3 | 1.3 |
| Statement c): Answer Missing | 9.4 | 5.0 | 13.8 |
| Statement d): Strongly Disagree | 1.3 | 1.3 | 1.3 |
| Statement d): Disagree | 3.8 | 1.3 | 6.3 |
| Statement d): Neutral | 5.6 | 5.0 | 6.3 |
| Statement d): Agree | 23.1 | 26.3 | 20.0 |
| Statement d): Strongly Agree | 56.3 | 60.0 | 52.5 |
| Statement d): Not Applicable | 1.3 | 1.3 | 1.3 |
| Statement d): Answer Missing | 8.8 | 5.0 | 12.5 |
| Statement e): Strongly Disagree | 1.3 | 1.3 | 1.3 |
| Statement e): Disagree | 1.9 | 1.3 | 2.5 |
| Statement e): Neutral | 8.8 | 11.3 | 6.3 |
| Statement e): Agree | 21.9 | 21.3 | 22.5 |
| Statement e): Strongly Agree | 55.0 | 58.8 | 51.3 |
| Statement e): Not Applicable | 1.9 | 1.3 | 2.5 |
| Statement e): Answer Missing | 9.4 | 5.0 | 13.8 |
| Statement f): Strongly Disagree | 0.6 | 0.0 | 1.3 |
| Statement f): Disagree | 4.4 | 3.8 | 5.0 |
| Statement f): Neutral | 11.9 | 16.3 | 7.5 |
| Statement f): Agree | 24.4 | 20.0 | 28.8 |
| Statement f): Strongly Agree | 48.1 | 53.8 | 42.5 |
| Statement f): Not Applicable | 1.3 | 1.3 | 1.3 |
| Statement f): Answer Missing | 9.4 | 5.0 | 13.8 |
| Statement g): Strongly Disagree | 0.6 | 0.0 | 1.3 |
| Statement g): Disagree | 0.0 | 0.0 | 0.0 |
| Statement g): Neutral | 6.9 | 8.8 | 5.0 |
| Statement g): Agree | 31.3 | 30.0 | 32.5 |
| Statement g): Strongly Agree | 48.8 | 52.5 | 45.0 |
| Statement g): Not Applicable | 3.1 | 3.8 | 2.5 |
| Statement g): Answer Missing | 9.4 | 5.0 | 13.8 |
Healthcare professionals (HCPs) who prepared study treatment within the pharmacy/drug preparation area responded at Cycle 6 of the Treatment Cross-Over Period to the following HCPQ-Drug Preparation Room Questions 3 and 4: "Looking back over the Perjeta-Herceptin treatment sessions, please indicate based on your opinion which administration method: Q3. Was quickest from start to end of preparation to finish of administration (excluding observation period)?; Q4. Required less resource use for preparation and administration, for example nursing time, facility costs, equipment etc?" The three available response options were: P+H IV, FDC SC, and No Difference.
| Percentage of HCPs | All Healthcare Professionals | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Q3. Answer: FDC SC | 87.5 | 92.5 | 82.5 |
| Q3. Answer: P+H IV | 0.6 | 0.0 | 1.3 |
| Q3. Answer: No Difference | 1.3 | 1.3 | 1.3 |
| Q3. Answer: Missing | 10.6 | 6.3 | 15.0 |
| Q4. Answer: FDC SC | 86.9 | 93.8 | 80.0 |
| Q4. Answer: P+H IV | 0.0 | 0.0 | 0.0 |
| Q4. Answer: No Difference | 2.5 | 0.0 | 5.0 |
| Q4. Answer: Missing | 10.6 | 6.3 | 15.0 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 74.21 ± 16.79 | 71.62 ± 17.98 | 76.77 ± 15.22 |
| Change from BL at Cycle 3 Day 1 | 0.27 ± 15.72 | 0.54 ± 16.63 | 0.00 ± 14.88 |
| Change from BL at Cycle 6 Day 1 | -0.05 ± 18.38 | 1.10 ± 20.25 | -1.16 ± 16.44 |
| Change from BL at Cycle 15 or Last Treatment Cycle | 2.29 ± 17.05 | 2.82 ± 16.30 | 1.76 ± 17.87 |
| Change from BL at 1.5 Years | 6.79 ± 19.38 | 7.18 ± 21.73 | 6.42 ± 16.92 |
| Change from BL at 2 Years | 5.14 ± 18.45 | 6.16 ± 19.45 | 4.11 ± 17.46 |
| Change from BL at 3 Years | 6.89 ± 18.45 | 7.23 ± 16.85 | 6.54 ± 20.12 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 86.16 ± 14.48 | 84.22 ± 14.91 | 88.08 ± 13.86 |
| Change from BL at Cycle 3 Day 1 | 0.67 ± 12.08 | 1.77 ± 12.97 | -0.42 ± 11.09 |
| Change from BL at Cycle 6 Day 1 | 1.20 ± 14.46 | 1.93 ± 16.61 | 0.51 ± 12.11 |
| Change from BL at Cycle 15 or Last Treatment Cycle | 2.54 ± 15.79 | 3.85 ± 13.65 | 1.22 ± 17.69 |
| Change from BL at 1.5 Years | 4.74 ± 15.71 | 5.44 ± 17.29 | 4.05 ± 14.08 |
| Change from BL at 2 Years | 3.97 ± 16.32 | 4.38 ± 18.57 | 3.56 ± 13.84 |
| Change from BL at 3 Years | 2.51 ± 14.67 | 3.33 ± 13.99 | 1.64 ± 15.41 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 78.30 ± 25.76 | 79.54 ± 25.45 | 77.08 ± 26.17 |
| Change from BL at Cycle 3 Day 1 | 6.71 ± 25.37 | 3.80 ± 24.01 | 9.58 ± 26.49 |
| Change from BL at Cycle 6 Day 1 | 7.42 ± 26.12 | 6.36 ± 24.03 | 8.44 ± 28.10 |
| Change from BL at Cycle 15 or Last Treatment Cycle | 9.62 ± 29.60 | 6.81 ± 24.00 | 12.44 ± 34.24 |
| Change from BL at 1.5 Years | 13.24 ± 30.00 | 9.49 ± 29.31 | 16.89 ± 30.41 |
| Change from BL at 2 Years | 11.30 ± 30.07 | 11.64 ± 29.22 | 10.96 ± 31.08 |
| Change from BL at 3 Years | 10.40 ± 29.13 | 8.09 ± 26.78 | 12.82 ± 31.43 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 82.08 ± 17.72 | 82.07 ± 16.99 | 82.08 ± 18.52 |
| Change from BL at Cycle 3 Day 1 | 0.05 ± 15.92 | -1.28 ± 15.26 | 1.35 ± 16.53 |
| Change from BL at Cycle 6 Day 1 | 0.32 ± 18.70 | 0.99 ± 20.04 | -0.32 ± 17.42 |
| Change from BL at Cycle 15 or Last Treatment Cycle | 0.65 ± 19.60 | -1.17 ± 15.77 | 2.46 ± 22.77 |
| Change from BL at 1.5 Years | 2.45 ± 22.47 | 0.93 ± 23.05 | 3.94 ± 21.95 |
| Change from BL at 2 Years | 1.86 ± 23.78 | 2.74 ± 21.61 | 0.99 ± 25.89 |
| Change from BL at 3 Years | 2.38 ± 23.78 | 3.55 ± 21.08 | 1.15 ± 26.43 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 85.22 ± 18.37 | 85.86 ± 17.92 | 84.58 ± 18.90 |
| Change from BL at Cycle 3 Day 1 | -0.95 ± 19.21 | -0.64 ± 17.08 | -1.25 ± 21.18 |
| Change from BL at Cycle 6 Day 1 | -2.47 ± 20.44 | -3.29 ± 18.86 | -1.69 ± 21.94 |
| Change from BL at Cycle 15 or Last Treatment Cycle | -4.69 ± 22.58 | -7.75 ± 21.79 | -1.64 ± 23.09 |
| Change from BL at 1.5 Years | -1.94 ± 21.31 | -3.47 ± 20.16 | -0.45 ± 22.41 |
| Change from BL at 2 Years | -1.03 ± 21.10 | -2.51 ± 20.54 | 0.46 ± 21.69 |
| Change from BL at 3 Years | -3.01 ± 23.64 | -2.45 ± 20.42 | -3.59 ± 26.76 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 79.01 ± 21.79 | 77.99 ± 22.39 | 80.00 ± 21.28 |
| Change from BL at Cycle 3 Day 1 | 6.26 ± 22.60 | 5.41 ± 24.40 | 7.08 ± 20.84 |
| Change from BL at Cycle 6 Day 1 | 4.44 ± 22.87 | 6.44 ± 25.39 | 2.53 ± 20.16 |
| Change from BL at Cycle 15 or Last Treatment Cycle | 7.80 ± 23.87 | 9.05 ± 23.86 | 6.57 ± 23.98 |
| Change from BL at 1.5 Years | 12.41 ± 24.20 | 12.21 ± 29.41 | 12.61 ± 18.05 |
| Change from BL at 2 Years | 13.68 ± 24.19 | 15.28 ± 25.29 | 12.10 ± 23.12 |
| Change from BL at 3 Years | 12.63 ± 24.46 | 11.94 ± 25.76 | 13.33 ± 23.24 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 22.01 ± 18.90 | 24.47 ± 19.28 | 19.58 ± 18.31 |
| Change from BL at Cycle 3 Day 1 | 1.29 ± 16.35 | -0.14 ± 17.66 | 2.71 ± 14.92 |
| Change from BL at Cycle 6 Day 1 | 0.50 ± 19.22 | -3.22 ± 17.85 | 4.08 ± 19.91 |
| Change from BL at Cycle 15 or Last Treatment Cycle | -2.11 ± 21.46 | -3.44 ± 18.36 | -0.78 ± 24.22 |
| Change from BL at 1.5 Years | -7.76 ± 19.59 | -9.26 ± 20.43 | -6.31 ± 18.76 |
| Change from BL at 2 Years | -5.25 ± 24.49 | -6.54 ± 25.51 | -3.96 ± 23.52 |
| Change from BL at 3 Years | -5.43 ± 22.58 | -7.68 ± 21.66 | -3.08 ± 23.45 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 2.73 ± 8.57 | 2.11 ± 7.24 | 3.33 ± 9.71 |
| Change from BL at Cycle 3 Day 1 | 0.84 ± 10.74 | 0.21 ± 9.80 | 1.46 ± 11.62 |
| Change from BL at Cycle 6 Day 1 | 0.75 ± 11.61 | 1.54 ± 11.92 | 0.00 ± 11.32 |
| Change from BL at Cycle 15 or Last Treatment Cycle | 1.17 ± 11.34 | 1.88 ± 12.13 | 0.47 ± 10.53 |
| Change from BL at 1.5 Years | -0.23 ± 11.41 | 0.46 ± 11.18 | -0.90 ± 11.67 |
| Change from BL at 2 Years | -0.68 ± 11.05 | -0.23 ± 11.28 | -1.14 ± 10.88 |
| Change from BL at 3 Years | -0.75 ± 10.83 | -1.23 ± 9.69 | -0.26 ± 11.97 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 16.04 ± 22.26 | 17.72 ± 24.94 | 14.38 ± 19.26 |
| Change from BL at Cycle 3 Day 1 | 0.21 ± 25.02 | 0.00 ± 27.86 | 0.42 ± 22.02 |
| Change from BL at Cycle 6 Day 1 | 0.43 ± 23.34 | -2.41 ± 25.92 | 3.16 ± 20.34 |
| Change from BL at Cycle 15 or Last Treatment Cycle | -1.17 ± 25.85 | -2.82 ± 25.04 | 0.47 ± 26.72 |
| Change from BL at 1.5 Years | -1.26 ± 28.84 | -1.62 ± 33.47 | -0.90 ± 23.71 |
| Change from BL at 2 Years | -3.08 ± 26.91 | -1.83 ± 30.25 | -4.34 ± 23.25 |
| Change from BL at 3 Years | -2.13 ± 28.23 | -1.72 ± 26.88 | -2.56 ± 29.79 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 5.87 ± 15.25 | 6.75 ± 15.45 | 5.00 ± 15.09 |
| Change from BL at Cycle 3 Day 1 | 0.63 ± 13.24 | -0.42 ± 14.61 | 1.67 ± 11.74 |
| Change from BL at Cycle 6 Day 1 | 3.01 ± 15.83 | 1.32 ± 15.81 | 4.64 ± 15.77 |
| Change from BL at Cycle 15 or Last Treatment Cycle | 1.88 ± 17.65 | 1.41 ± 19.05 | 2.35 ± 16.26 |
| Change from BL at 1.5 Years | 0.68 ± 13.82 | -0.46 ± 10.46 | 1.80 ± 16.45 |
| Change from BL at 2 Years | 1.83 ± 14.00 | 1.83 ± 16.56 | 1.83 ± 10.96 |
| Change from BL at 3 Years | 1.50 ± 14.13 | 1.47 ± 13.42 | 1.54 ± 14.94 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 22.22 ± 25.34 | 21.94 ± 24.97 | 22.50 ± 25.86 |
| Change from BL at Cycle 3 Day 1 | 1.26 ± 27.01 | 2.95 ± 26.25 | -0.42 ± 27.81 |
| Change from BL at Cycle 6 Day 1 | 1.72 ± 29.86 | 5.26 ± 29.34 | -1.69 ± 30.15 |
| Change from BL at Cycle 15 or Last Treatment Cycle | -0.94 ± 31.75 | 3.76 ± 32.15 | -5.63 ± 30.85 |
| Change from BL at 1.5 Years | -0.23 ± 30.95 | 1.85 ± 30.07 | -2.25 ± 31.85 |
| Change from BL at 2 Years | 2.97 ± 33.89 | 6.85 ± 35.56 | -0.91 ± 31.90 |
| Change from BL at 3 Years | 0.00 ± 34.08 | 1.47 ± 33.79 | -1.54 ± 34.58 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 10.06 ± 19.40 | 8.44 ± 14.59 | 11.67 ± 23.18 |
| Change from BL at Cycle 3 Day 1 | 0.21 ± 21.38 | 3.38 ± 23.02 | -2.92 ± 19.26 |
| Change from BL at Cycle 6 Day 1 | -0.86 ± 18.20 | 0.00 ± 18.86 | -1.69 ± 17.62 |
| Change from BL at Cycle 15 or Last Treatment Cycle | -5.40 ± 20.49 | -4.69 ± 17.18 | -6.10 ± 23.44 |
| Change from BL at 1.5 Years | -6.16 ± 19.96 | -4.63 ± 20.41 | -7.66 ± 19.54 |
| Change from BL at 2 Years | -4.34 ± 18.47 | -5.48 ± 15.73 | -3.20 ± 20.91 |
| Change from BL at 3 Years | -6.02 ± 19.61 | -5.39 ± 15.89 | -6.67 ± 22.97 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 9.01 ± 19.37 | 8.44 ± 16.42 | 9.58 ± 21.99 |
| Change from BL at Cycle 3 Day 1 | -1.68 ± 16.69 | 0.00 ± 15.10 | -3.33 ± 18.06 |
| Change from BL at Cycle 6 Day 1 | -0.86 ± 19.35 | 0.88 ± 20.35 | -2.53 ± 18.31 |
| Change from BL at Cycle 15 or Last Treatment Cycle | -0.70 ± 21.18 | 0.00 ± 20.31 | -1.41 ± 22.14 |
| Change from BL at 1.5 Years | 0.23 ± 23.97 | 0.00 ± 17.69 | 0.45 ± 28.93 |
| Change from BL at 2 Years | 1.60 ± 26.93 | 5.94 ± 26.26 | -2.74 ± 27.08 |
| Change from BL at 3 Years | 1.50 ± 23.52 | 0.49 ± 20.36 | 2.56 ± 26.55 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 10.48 ± 21.59 | 12.24 ± 22.76 | 8.75 ± 20.36 |
| Change from BL at Cycle 3 Day 1 | 7.17 ± 27.22 | 4.70 ± 25.04 | 9.58 ± 29.14 |
| Change from BL at Cycle 6 Day 1 | 4.95 ± 24.26 | 4.39 ± 23.31 | 5.49 ± 25.28 |
| Change from BL at Cycle 15 or Last Treatment Cycle | 2.58 ± 26.06 | 2.82 ± 25.66 | 2.35 ± 26.62 |
| Change from BL at 1.5 Years | -6.39 ± 22.25 | -8.33 ± 23.57 | -4.50 ± 20.88 |
| Change from BL at 2 Years | -6.85 ± 23.79 | -8.22 ± 26.52 | -5.48 ± 20.80 |
| Change from BL at 3 Years | -7.52 ± 23.79 | -9.80 ± 25.79 | -5.13 ± 21.43 |
The EORTC QLQ-C30 questionnaire consisted of 30 questions covering treatment-related symptoms, functioning, and GHS/HRQoL. Questions were answered by participants on a scale from 1 to 4 or 1 to 7. Raw scores were transformed to scale scores that ranged from 0 to 100 where a higher scale score indicating a higher response (i.e., on the functioning and GHS/QoL scales a higher score meant better functioning/QoL, whereas on the symptom scales a higher score meant greater \[worse\] symptoms). The EORTC QLQ-C30 data was scored according to the EORTC scoring manual (Fayers 2001). In the event of incomplete data, for all questionnaire subscales, if more than 50% of the constituent items are completed, a pro-rated score was to be computed consistent with the scoring manuals and published validation reports. For subscales with less than 50% of the items completed, the subscale was to be considered as missing.
| score on a scale | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Baseline (BL): Value at Visit | 22.85 ± 27.59 | 23.63 ± 27.30 | 22.08 ± 28.04 |
| Change from BL at Cycle 3 Day 1 | -2.95 ± 22.38 | -2.99 ± 20.23 | -2.92 ± 24.42 |
| Change from BL at Cycle 6 Day 1 | -2.15 ± 22.69 | -4.39 ± 20.61 | 0.00 ± 24.46 |
| Change from BL at Cycle 15 or Last Treatment Cycle | -8.45 ± 25.24 | -8.45 ± 25.02 | -8.45 ± 25.65 |
| Change from BL at 1.5 Years | -12.56 ± 28.27 | -13.89 ± 30.00 | -11.26 ± 26.62 |
| Change from BL at 2 Years | -14.38 ± 27.93 | -15.98 ± 27.84 | -12.79 ± 28.13 |
| Change from BL at 3 Years | -11.53 ± 30.99 | -14.71 ± 32.26 | -8.21 ± 29.48 |
Investigators used the NCI CTCAE v4.0 grading scale for assessing adverse event (AE) severity; if not listed, AE severity was graded as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe or medically significant; Grade 4 = life-threatening; Grade 5 = death related to AE. Severity and seriousness are not synonymous and investigators independently assessed these criteria for each AE. Investigators also determined whether an AE was considered to be related to the study drug. Adverse events to monitor were defined based on known risks associated with the study drugs and included: hypersensitivity reactions, administration-related reactions (ARRs), cardiac dysfunction, diarrhea grade ≥3, rash/skin reactions, mucositis, interstitial lung disease (ILD), (febrile) neutropenia, pulmonary events that may occur as a result of an ARR, and pregnancy/neonatal related. Multiple occurrences of AEs were counted only once per participant. LVEF = left ventricular ejection fraction
| Participants | Arm A: Treatment With P+H IV (Cycles 1 to 3) | Arm A: Treatment With PH FDC SC (Cycles 4 to 6) | Arm B: Treatment With PH FDC SC (Cycles 1 to 3) | Arm B: Treatment With P+H IV (Cycles 4 to 6) |
|---|---|---|---|---|
| Any Adverse Event (AE) | 62 | 60 | 62 | 51 |
| AE with Fatal Outcome | 0 | 0 | 0 | 0 |
| Related AE with Fatal Outcome | 0 | 0 | 0 | 0 |
| Grade 3 to 5 AE | 1 | 1 | 3 | 4 |
| Related Grade 3 to 5 AE | 1 | 0 | 1 | 0 |
| Cardiac AE (Including LVEF Events) | 1 | 2 | 3 | 2 |
| Serious AE | 1 | 1 | 1 | 5 |
| Anaphylaxis and Hypersensitivity AE, All Grades | 0 | 2 | 1 | 0 |
| Anaphylaxis and Hypersensitivity AE, Grade ≥3 | 0 | 0 | 0 | 0 |
| Administration Related Reaction (ARR), All Grades | 7 | 14 | 24 | 2 |
| Administration Related Reaction (ARR), Grade ≥3 | 0 | 0 | 0 | 0 |
| Cardiac Dysfunction AE, All Grades | 2 | 1 | 3 | 3 |
| Cardiac Dysfunction AE, Grade ≥3 | 1 | 0 | 0 | 0 |
| Diarrhea Grade ≥3 | 0 | 0 | 1 | 0 |
| Rash/Skin Reactions | 0 | 0 | 0 | 0 |
| Mucositis | 0 | 0 | 0 | 0 |
| Pulmonary Events (ARR), All Grades | 18 | 8 | 4 | 8 |
| Pulmonary Events (ARR), Grade ≥3 | 0 | 0 | 1 | 0 |
| Pregnancy and Neonatal Related AEs, All Grades | 0 | 0 | 1 | 0 |
| Pregnancy and Neonatal Related AEs, Grade ≥3 | 0 | 0 | 0 | 0 |
| Interstitial Lung Disease (ILD) | 0 | 0 | 0 | 0 |
| Neutropenia/Febrile Neutropenia, All Grades | 4 | 1 | 2 | 3 |
| Neutropenia/Febrile Neutropenia, Grade ≥3 | 0 | 0 | 0 | 0 |
| Local Infusion Site Reaction | 1 | 0 | 0 | 0 |
| Systemic Infusion Site Reaction | 5 | 0 | 0 | 1 |
| Local Injection Site Reaction | 0 | 12 | 24 | 0 |
| Systemic Injection Site Reaction | 0 | 2 | 1 | 0 |
| AE Leading to Any Study Treatment Discontinuation | 0 | 1 | 0 | 0 |
| AE Leading to PH FDC SC Discontinuation | 0 | 1 | 0 | 0 |
| AE Leading to Pertuzumab IV Discontinuation | 0 | 0 | 0 | 0 |
| AE Leading to Trastuzumab IV Discontinuation | 0 | 0 | 0 | 0 |
| AE Leading to Any Study Treatment Interruption or Dose Reduction | 1 | 0 | 2 | 3 |
Investigators used the NCI CTCAE v4.0 grading scale for assessing adverse event (AE) severity; if not listed, AE severity was graded as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe or medically significant; Grade 4 = life-threatening; Grade 5 = death related to AE. Severity and seriousness are not synonymous and investigators independently assessed these criteria for each AE. Investigators also determined whether an AE was considered to be related to the study drug. Adverse events to monitor were defined based on known risks associated with the study drugs and included: hypersensitivity reactions, administration-related reactions (ARRs), cardiac dysfunction, diarrhea grade ≥3, rash/skin reactions, mucositis, interstitial lung disease (ILD), (febrile) neutropenia, pulmonary events that may occur as a result of an ARR, and pregnancy/neonatal related. Multiple occurrences of AEs were counted only once per participant. LVEF = left ventricular ejection fraction
| Participants | P+H IV: Treatment Cross-Over Period | PH FDC SC: Treatment Cross-Over Period | P+H IV: Treatment Continuation Period | PH FDC SC: Treatment Continuation Period |
|---|---|---|---|---|
| Any Adverse Event (AE) | 113 | 122 | 14 | 92 |
| AE with Fatal Outcome | 0 | 0 | 0 | 0 |
| Related AE with Fatal Outcome | 0 | 0 | 0 | 0 |
| Grade 3 to 5 AE | 5 | 4 | 2 | 7 |
| Related Grade 3 to 5 AE | 1 | 1 | 0 | 0 |
| Cardiac AE (Including LVEF Events) | 3 | 5 | 1 | 1 |
| Serious AE | 6 | 2 | 0 | 4 |
| Anaphylaxis and Hypersensitivity AE, All Grades | 0 | 3 | 0 | 2 |
| Anaphylaxis and Hypersensitivity AE, Grade ≥3 | 0 | 0 | 0 | 0 |
| Administration Related Reaction AE, All Grades | 9 | 38 | 1 | 16 |
| Administration Related Reaction AE, Grade ≥3 | 0 | 0 | 0 | 0 |
| Cardiac Dysfunction AE, All Grades | 5 | 4 | 1 | 2 |
| Cardiac Dysfunction AE, Grade ≥3 | 1 | 0 | 0 | 0 |
| Diarrhea Grade ≥3 | 0 | 1 | 0 | 0 |
| Rash/Skin Reactions | 0 | 0 | 0 | 0 |
| Mucositis | 0 | 0 | 0 | 0 |
| Pulmonary Events (ARR), All Grades | 26 | 12 | 5 | 13 |
| Pulmonary Events (ARR), Grade ≥3 | 0 | 1 | 0 | 0 |
| Pregnancy and Neonatal Related AEs, All Grades | 0 | 1 | 0 | 0 |
| Pregnancy and Neonatal Related AEs, Grade ≥3 | 0 | 0 | 0 | 0 |
| Interstitial Lung Disease (ILD), All Grades | 0 | 0 | 0 | 1 |
| Interstitial Lung Disease (ILD), Grade ≥3 | 0 | 0 | 0 | 0 |
| Neutropenia/Febrile Neutropenia, All Grades | 7 | 3 | 1 | 5 |
| Neutropenia/Febrile Neutropenia, Grade ≥3 | 0 | 0 | 0 | 1 |
| Local Infusion Site Reaction | 1 | 0 | 0 | 0 |
| Systemic Infusion Site Reaction | 6 | 0 | 1 | 0 |
| Local Injection Site Reaction | 0 | 36 | 0 | 13 |
| Systemic Injection Site Reaction | 0 | 3 | 0 | 2 |
| AE Leading to Any Study Treatment Discontinuation | 0 | 1 | 1 | 0 |
| AE Leading to PH FDC SC Discontinuation | 0 | 1 | 0 | 0 |
| AE Leading to Pertuzumab IV Discontinuation | 0 | 0 | 1 | 0 |
| AE Leading to Trastuzumab IV Discontinuation | 0 | 0 | 1 | 0 |
| AE Leading to Any Study Treatment Interruption or Dose Reduction | 4 | 2 | 1 | 8 |
Heart failure is defined as a disorder characterized by the inability of the heart to pump blood at an adequate volume to meet tissue metabolic requirements, or, the ability to do only at an elevation in the filling pressure. Any adverse event of symptomatic left ventricular systolic dysfunction (LVSD; also referred to as heart failure) occurring during the study was to be reported as a serious adverse event.
| Participants | P+H IV: Treatment Cross-Over Period | PH FDC SC: Treatment Cross-Over Period | P+H IV: Treatment Continuation Period | PH FDC SC: Treatment Continuation Period |
|---|---|---|---|---|
| Number of Participants With at Least One Event of Heart Failure With the FDC SC and IV Formulations During the Treatment Cross-Over and Treatment Continuation Periods | 0 | 0 | 0 | 0 |
Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. All participants who enrolled in this study must have had a baseline LVEF ≥55%. Verbatim description of adverse events was mapped to Medical Dictionary for Regulatory Activities (MedDRA) version 25.1. The MedDRA preferred term of 'ejection fraction decreased' is defined as an LVEF decrease of at least 10 percentage points from baseline and to below 50%.
| Participants | P+H IV: Treatment Cross-Over Period | PH FDC SC: Treatment Cross-Over Period | P+H IV: Treatment Continuation Period | PH FDC SC: Treatment Continuation Period |
|---|---|---|---|---|
| Number of Participants With at Least One Event of Ejection Fraction Decreased With the FDC SC and IV Formulations During the Treatment Cross-Over and Treatment Continuation Periods | 3 | 4 | 1 | 0 |
The number of participants at any post-baseline timepoint with abnormal readings outside the normal range for vital signs of diastolic and systolic blood pressure, pulse rate, respiratory rate, and body temperature were summarized according the specified direction of the abnormal reading (high or low). The number analyzed (denominator) in the results table represents participants without the specified abnormal vital sign at baseline. Not every vital sign abnormality qualified as an adverse event (AE). A vital sign result must have been reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption, or treatment discontinuation); resulted in a medical intervention or a change in concomitant therapy; or, was clinically significant in the investigator's judgment.
| Participants | Arm A: Treatment With P+H IV (Cycles 1 to 3) | Arm A: Treatment With PH FDC SC (Cycles 4 to 6) | Arm B: Treatment With PH FDC SC (Cycles 1 to 3) | Arm B: Treatment With P+H IV (Cycles 4 to 6) | P+H IV: Treatment Continuation Period | PH FDC SC: Treatment Continuation Period |
|---|---|---|---|---|---|---|
| Diastolic Blood Pressure - Low | 0 | 0 | 0 | 0 | 0 | 0 |
| Diastolic Blood Pressure - High | 2 | 2 | 0 | 0 | 0 | 3 |
| Systolic Blood Pressure - Low | 0 | 0 | 0 | 0 | 0 | 0 |
| Systolic Blood Pressure - High | 8 | 7 | 3 | 3 | 1 | 12 |
| Pulse Rate - Low | 0 | 0 | 0 | 0 | 0 | 0 |
| Pulse Rate - High | 1 | 0 | 0 | 1 | 1 | 1 |
| Respiratory Rate - Low | 0 | 0 | 0 | 0 | 0 | 0 |
| Respiratory Rate - High | 1 | 0 | 2 | 2 | 0 | 4 |
| Temperature - Low | 22 | 17 | 10 | 13 | 4 | 34 |
| Temperature - High | 0 | 0 | 1 | 0 | 0 | 0 |
Laboratory data for targeted chemistry and hematology parameters were classified according to the NCI CTCAE v4.0; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). The results show the shifts in the number of participants with Grade 0-2 at baseline to Grade 3-4 post-baseline; those with missing baseline values were counted as Grade 0-2 at baseline. Not every laboratory abnormality qualified as an adverse event, only if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment (e.g., dosage modification, treatment interruption, or treatment discontinuation); resulted in a medical intervention or a change in concomitant therapy; or, was clinically significant in the investigator's judgment. SGOT/AST = aspartate aminotransferase; SGPT/ALT = alanine aminotransferase
| Participants | Arm A: Treatment With P+H IV (Cycles 1 to 3) | Arm A: Treatment With PH FDC SC (Cycles 4 to 6) | Arm B: Treatment With PH FDC SC (Cycles 1 to 3) | Arm B: Treatment With P+H IV (Cycles 4 to 6) | P+H IV: Treatment Continuation Period | PH FDC SC: Treatment Continuation Period |
|---|---|---|---|---|---|---|
| Alkaline Phosphatase - High | 0 | 0 | 0 | 0 | 0 | 0 |
| SGPT/ALT - High | 0 | 0 | 0 | 0 | 0 | 0 |
| SGOT/AST - High | 0 | 0 | 0 | 0 | 0 | 0 |
| Creatinine - High | 0 | 0 | 0 | 0 | 0 | 0 |
| Bilirubin, Total - High | 0 | 0 | 0 | 0 | 0 | 0 |
| Hemoglobin - Low | 0 | 0 | 0 | 0 | 0 | 0 |
| Hemoglobin - High | 0 | 0 | 0 | 0 | 0 | 0 |
| Neutrophils, Total, Abs - Low | 0 | 0 | 0 | 0 | 0 | 2 |
| Platelet - Low | 0 | 0 | 0 | 0 | 0 | 0 |
| Total Leukocyte Count - Low | 0 | 0 | 0 | 0 | 0 | 1 |
| Total Leukocyte Count - High | 0 | 0 | 0 | 0 | 0 | 0 |
Overall survival (OS) is defined as the time from randomization to death due to any cause. The number of participants who had an OS event (i.e., died) while on study is reported.
| Participants | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Number of Participants With an Event for Overall Survival, Overall and by Treatment Sequence | 2 | 2 | 0 |
Overall survival is defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the time of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization +1 day. Kaplan-Meier methodology was used to estimate the percentage of participants who were alive (event-free) at 12, 24, and 36 months.
| Percentage of participants | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| 12 Months | 100.00 (100.00 to 100.00) | 100.00 (100.00 to 100.00) | 100.00 (100.00 to 100.00) |
| 24 Months | 99.36 (98.12 to 100.00) | 98.73 (96.27 to 100.00) | 100.00 (100.00 to 100.00) |
| 36 Months | 98.71 (96.92 to 100.00) | 97.44 (93.93 to 100.00) | 100.00 (100.00 to 100.00) |
Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Second primary non-breast invasive cancer (with the exception of non-melanoma skin cancers and in situ carcinoma of any site) was included as an event.
| Participants | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Number of Participants With an Event for Invasive Disease-Free Survival Including Second Primary Non-Breast Cancer, Overall and by Treatment Sequence | 12 | 7 | 5 |
Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Second primary non-breast invasive cancer (with the exception of non-melanoma skin cancers and in situ carcinoma of any site) was included as an event. Participants who had not experienced invasive disease at the time of analysis were censored: i) at the time of the last clinical breast examination if they had post-baseline clinical breast examination; ii) on the date of randomization +1 day if no post-baseline clinical breast examination. Kaplan-Meier methodology was used to estimate the percentage of participants who were event-free at 12, 24, and 36 months.
| Percentage of participants | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| 12 Months | 97.46 (95.00 to 99.92) | 94.94 (90.10 to 99.77) | 100.00 (100.00 to 100.00) |
| 24 Months | 94.87 (91.40 to 98.33) | 92.37 (86.50 to 98.24) | 97.38 (93.80 to 100.00) |
| 36 Months | 93.53 (89.65 to 97.41) | 91.05 (84.72 to 97.38) | 96.03 (91.63 to 100.00) |
Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) were not counted as recurrence.
| Participants | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Number of Participants With an Event for Invasive Disease-Free Survival, Overall and by Treatment Sequence | 11 | 6 | 5 |
Invasive Disease-Free Survival is defined as the time from randomization to the first occurrence of one of the following events: ipsilateral invasive breast tumour recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) were not counted as recurrence. Participants who had not experienced invasive disease at the time of analysis were censored: i) at the time of the last clinical breast examination if they had post-baseline clinical breast examination; ii) on the date of randomization +1 day if no post-baseline clinical breast examination. Kaplan-Meier methodology was used to estimate the percentage of participants who were event-free at 12, 24, and 36 months.
| Percentage of participants | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| 12 Months | 98.10 (95.96 to 100.00) | 96.20 (91.99 to 100.00) | 100.00 (100.00 to 100.00) |
| 24 Months | 95.51 (92.25 to 98.76) | 93.64 (88.24 to 99.03) | 97.38 (93.80 to 100.00) |
| 36 Months | 94.17 (90.47 to 97.87) | 92.32 (86.41 to 98.23) | 96.03 (91.63 to 100.00) |
Distant disease-free survival (DDFS) is defined as the time from randomization to the date of distant breast cancer recurrence (i.e., evidence of breast cancer in any anatomic site other than for ipsilateral \[loco-regional\] invasive breast cancer recurrence that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer).
| Participants | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| Number of Participants With an Event for Distant Disease-Free Survival, Overall and by Treatment Sequence | 9 | 5 | 4 |
Distant disease-free survival (DDFS) is defined as the time from randomization to the date of distant breast cancer recurrence (i.e., evidence of breast cancer in any anatomic site other than for ipsilateral \[loco-regional\] invasive breast cancer recurrence that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer). Participants who had not experienced invasive disease at the time of analysis were censored: i) at the time of the last clinical breast examination if they had post-baseline clinical breast examination; ii) on the date of randomization +1 day if no post-baseline clinical breast examination. Kaplan-Meier methodology was used to estimate the percentage of participants who were event-free at 12, 24, and 36 months.
| Percentage of participants | All Participants | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|---|
| 12 Months | 98.73 (96.98 to 100.00) | 97.47 (94.00 to 100.00) | 100.00 (100.00 to 100.00) |
| 24 Months | 96.14 (93.11 to 99.17) | 94.90 (90.04 to 99.77) | 97.38 (93.80 to 100.00) |
| 36 Months | 94.80 (91.30 to 98.31) | 93.58 (88.14 to 99.03) | 96.03 (91.63 to 100.00) |
Collected over AEs and deaths reporting timeframes during study treatment: Cross-Over Period: 3 cycles (cyc) of P+H IV & 3 cyc of PH FDC SC; Continuation Period: from Cyc 7 to 18 total cyc of P+H IV or PH FDC SC (1 cyc = 21 days); All Participants: from first dose through 28 days after last dose of study treatment (up to 1 year). Follow-up period: AEs reported from 29 days up to 7 months after the last dose of study treatment; deaths reported from 29 days after last dose until the end of follow-up (≥3 years).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| P+H IV: Treatment Cross-Over Period | 0/160 (0%) | 6/160 (3.8%) | 62/160 (38.8%) |
| PH FDC SC: Treatment Cross-Over Period | 0/160 (0%) | 2/160 (1.3%) | 84/160 (52.5%) |
| P+H IV: Treatment Continuation Period | 0/21 (0%) | 0/21 (0%) | 10/21 (47.6%) |
| PH FDC SC: Treatment Continuation Period | 0/138 (0%) | 4/138 (2.9%) | 47/138 (34.1%) |
| All Participants: All Study Treatment Periods | 0/160 (0%) | 11/160 (6.9%) | 125/160 (78.1%) |
| Follow-Up Period | 2/159 (1.3%) | 1/159 (0.6%) | 2/159 (1.3%) |
| Event | P+H IV: Treatment Cross-Over Period | PH FDC SC: Treatment Cross-Over Period | P+H IV: Treatment Continuation Period | PH FDC SC: Treatment Continuation Period | All Participants: All Study Treatment Periods | Follow-Up Period |
|---|---|---|---|---|---|---|
| ErysipelasInfections and infestations | 1/160 | 0/160 | 0/21 | 2/138 | 2/160 | 0/159 |
| Device related infectionInfections and infestations | 1/160 | 0/160 | 0/21 | 1/138 | 2/160 | 0/159 |
| Ejection fraction decreasedInvestigations | 1/160 | 1/160 | 0/21 | 0/138 | 2/160 | 0/159 |
| Bronchopulmonary aspergillosisInfections and infestations | 0/160 | 0/160 | 0/21 | 1/138 | 1/160 | 0/159 |
| COVID-19Infections and infestations | 0/160 | 0/160 | 0/21 | 1/138 | 1/160 | 0/159 |
| Cardiac failureCardiac disorders | 0/160 | 0/160 | 0/21 | 0/138 | 0/160 | 1/159 |
| Breast cellulitisInfections and infestations | 1/160 | 0/160 | 0/21 | 0/138 | 1/160 | 0/159 |
| PneumoniaInfections and infestations | 1/160 | 0/160 | 0/21 | 0/138 | 1/160 | 0/159 |
| Upper respiratory tract infectionInfections and infestations | 1/160 | 0/160 | 0/21 | 0/138 | 1/160 | 0/159 |
| AsthmaRespiratory, thoracic and mediastinal disorders | 0/160 | 1/160 | 0/21 | 0/138 | 1/160 | 0/159 |
| Event | P+H IV: Treatment Cross-Over Period | PH FDC SC: Treatment Cross-Over Period | P+H IV: Treatment Continuation Period | PH FDC SC: Treatment Continuation Period | All Participants: All Study Treatment Periods | Follow-Up Period |
|---|---|---|---|---|---|---|
| Injection site reactionGeneral disorders | 0/160 | 36/160 | 0/21 | 13/138 | 44/160 | 0/159 |
| Radiation skin injuryInjury, poisoning and procedural complications | 27/160 | 17/160 | 0/21 | 1/138 | 44/160 | 0/159 |
| DiarrhoeaGastrointestinal disorders | 17/160 | 15/160 | 4/21 | 15/138 | 37/160 | 0/159 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 6/160 | 8/160 | 3/21 | 6/138 | 23/160 | 1/159 |
| RashSkin and subcutaneous tissue disorders | 2/160 | 3/160 | 3/21 | 2/138 | 10/160 | 0/159 |
| FatigueGeneral disorders | 8/160 | 9/160 | 1/21 | 7/138 | 19/160 | 0/159 |
| Hot flushVascular disorders | 6/160 | 9/160 | 0/21 | 3/138 | 16/160 | 0/159 |
| Bone painMusculoskeletal and connective tissue disorders | 0/160 | 0/160 | 2/21 | 0/138 | 2/160 | 0/159 |
| MyalgiaMusculoskeletal and connective tissue disorders | 6/160 | 3/160 | 2/21 | 1/138 | 12/160 | 1/159 |
| HeadacheNervous system disorders | 3/160 | 5/160 | 2/21 | 1/138 | 10/160 | 0/159 |
Intent-to-Treat (ITT) Population: includes all randomized participants, allocated to their randomized treatment arm, whether or not the assigned study treatment was received.
| Age, Continuous(Years) | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV | Total |
|---|---|---|---|
| Mean | 49.4 ± 11.6 | 48.2 ± 12.1 | 48.8 ± 11.8 |
| Sex: Female, Male(Participants) | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV | Total |
|---|---|---|---|
| Female | 80 | 80 | 160 |
| Male | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV | Total |
|---|---|---|---|
| Hispanic or Latino | 17 | 21 | 38 |
| Not Hispanic or Latino | 59 | 54 | 113 |
| Unknown or Not Reported | 4 | 5 | 9 |
| Race (NIH/OMB)(Participants) | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV | Total |
|---|---|---|---|
| American Indian or Alaska Native | 5 | 3 | 8 |
| Asian | 8 | 4 | 12 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 2 | 2 | 4 |
| White | 62 | 67 | 129 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 3 | 4 | 7 |
| Baseline Weight(kilograms (kg)) | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV | Total |
|---|---|---|---|
| Mean | 67.36 ± 12.08 | 70.21 ± 14.15 | 68.78 ± 13.20 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline(Participants) | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV | Total |
|---|---|---|---|
| ECOG Peformance Status 0 | 70 | 70 | 140 |
| ECOG Peformance Status 1 | 10 | 10 | 20 |
| Number of Cycles of Prior Neoadjuvant Pertuzumab IV and Trastuzumab IV(Participants) | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV | Total |
|---|---|---|---|
| <4 Cycles | 5 | 10 | 15 |
| ≥4 Cycles | 75 | 70 | 145 |
| Prior Neoadjuvant Chemotherapy Regimen(Participants) | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV | Total |
|---|---|---|---|
| Anthracyclines + Taxanes | 55 | 53 | 108 |
| Carboplatin + Taxanes | 22 | 23 | 45 |
| Taxanes Only | 3 | 4 | 7 |
2 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Ran from Dec 2018 to primary completion in Feb 2020, 14 months.
Results were first posted in Apr 2021, 1 year 2 months after primary completion.
Of 232 industry-sponsored phase 2 interventional studies under Breast Neoplasms, half reached primary completion within 34 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 53. This study's 14 months is below that.
Counting every sponsor, half of 1,302 studies reached it within 51 months; a quarter within 30 and three quarters within 82.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Dec 2023. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Pertuzumab