Study in Participants With Early-Stage or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2-Positive Breast Cancer to Evaluate Treatment With Trastuzumab Plus (+) Pertuzumab + Docetaxel Compared With Trastuzumab + Placebo + Docetaxel

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• Breast Neoplasms 12,544

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 329 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Study arms

• Experimental
  Trastuzumab, Pertuzumab, and Chemotherapy

  Prior to surgery: trastuzumab, pertuzumab, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC): trastuzumab and pertuzumab up to 1 year total.

  Drug: FEC Chemotherapy · Procedure: Surgery · Drug: Docetaxel · Drug: Pertuzumab · Drug: Trastuzumab

• Experimental
  Trastuzumab, Placebo, and Chemotherapy

  Prior to surgery: trastuzumab, placebo, and docetaxel for 4 cycles (1 cycle = 21 days). After surgery/FEC chemotherapy: trastuzumab and placebo up to 1 year total.

  Drug: FEC Chemotherapy · Procedure: Surgery · Drug: Docetaxel · Drug: Placebo · Drug: Trastuzumab

Interventions

• DrugFEC Chemotherapy

  Fluorouracil 500-600 milligrams per square meter (mg/m2), epirubicin 90-120 mg/m2, and cyclophosphamide 500-600 mg/m2 by intravenous (IV) infusion every 3 weeks for three cycles (Cycles 5-7). FEC chemotherapeutic agents will be administered following surgery on Day 1 of each specified cycle.

• ProcedureSurgery

  All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.

• DrugDocetaxel

  Docetaxel IV infusion in 3-week cycles. Neoadjuvant treatment: 75 mg/m2 for Cycles 1-4.

• DrugPertuzumab

  Pertuzumab IV infusion in 3-week cycles. Prior to surgery (neoadjuvant treatment): 840 milligrams (mg) loading dose for Cycle 1, followed by 420 mg for Cycles 2-4. After surgery and 3 cycles of FEC chemotherapy (adjuvant treatment): 840 mg loading dose for Cycle 8, followed by 420 mg for Cycles 9-20)

  Also known as: RO4368451

• DrugPlacebo

  Placebo by IV infusion in 3-week cycles as neoadjuvant treatment (Cycles 1-4)and as adjuvant treatment (Cycles 8-20)

• DrugTrastuzumab

  Trastuzumab IV infusion in 3-week cycles. Neoadjuvant treatment: 8 milligrams per kilogram (mg/kg) loading dose for Cycle 1, followed by 6 mg/kg for Cycles 2-4. Adjuvant treatment: 8 mg/kg loading dose for Cycle 8, followed by 6 mg/kg for Cycles 9-20.

  Also known as: RO0452317

Primary outcomes

1. Percentage of Participants With Total Pathologic Complete Response (tpCR) as Assessed by the Independent Review Committee (IRC)

   This tpCR was assessed by the IRC. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current American Joint Committee on Cancer \[AJCC\] staging system). The analysis was based on the ITT population with participants grouped by the treatment assigned at the time of randomization. Participants whose tpCR assessment was missing or invalid were counted as not achieving tpCR. The duration of one treatment cycle was 21 days; the administration of therapy in Cycle 5 did not occur until 2 weeks after surgery. The percentages have been rounded off to first decimal point.

   Time frame: At surgery (Cycle 4 Days 22-35)

Secondary outcomes

1. Percentage of Participants With tpCR as Assessed by the Local Pathologist

   This tpCR was assessed by the local pathologist. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current AJCC staging system). The analysis was based on the ITT population with participants grouped by the treatment assigned at the time of randomization. Participants whose tpCR assessment was missing or invalid were counted as not achieving tpCR. The duration of one treatment cycle was 21 days; the administration of therapy in Cycle 5 did not occur until 2 weeks after surgery. The percentages have been rounded off to first decimal point.

   Time frame: At surgery (Cycle 4 Days 22-35)

2. Percentage of Participants With Breast Pathologic Complete Response (bpCR), Defined as ypT0/is According to the AJCC Staging System as Assessed by the IRC

   This bpCR was assessed by the IRC. bpCR was defined as the absence of any residual invasive cancer on the hematoxylin and eosin evaluation of the resected breast specimen after completion of neoadjuvant therapy and surgery (that is, ypT0/is, in accordance with current AJCC staging system). The analysis was based on the ITT population with participants grouped by the treatment assigned at the time of randomization. Participants whose bpCR assessment was missing or invalid were counted as not achieving bpCR. The duration of one treatment cycle was 21 days; the administration of therapy in Cycle 5 did not occur until 2 weeks after surgery. The percentages have been rounded off to first decimal point.

   Time frame: At surgery (Cycle 4 Days 22-35)

3. Percentage of Participants With bpCR as Assessed by the Local Pathologist

   This bpCR was assessed by the local pathologist. bpCR was defined as the absence of any residual invasive cancer on the hematoxylin and eosin evaluation of the resected breast specimen after completion of neoadjuvant therapy and surgery (that is, ypT0/is in accordance with current AJCC staging system). The analysis was based on the ITT population with participants grouped by the treatment assigned at the time of randomization. Participants whose bpCR assessment was missing or invalid were counted as not achieving bpCR. The duration of one treatment cycle was 21 days; the administration of therapy in Cycle 5 did not occur until 2 weeks after surgery. The percentages have been rounded off to first decimal point.

   Time frame: At surgery (Cycle 4 Days 22-35)

4. Percentage of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) During Cycles 1-4, According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

   Clinical responses that include percentage of participants with a CR, PR, SD, or PD were determined by investigator during Cycles 1-4 (prior to surgery) on basis of RECIST version 1.1. CR=disappearance of all target lesions i.e., any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum during the study. PD=at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (nadir) with inclusion of baseline. Only participants with measurable disease at baseline were included in the analysis. 1 Cycle=21 days. The percentages have been rounded off to first decimal point.

   Time frame: At surgery (Cycle 4 Days 22-35)

5. Percentage of Participants With an Objective Response (CR or PR) During Cycles 1-4, According to RECIST Version 1.1

   An objective response was defined as the percentage of participants who achieved a CR or PR as the best tumor response during the neoadjuvant period (that is, during Cycles 1-4 prior to surgery), as determined by the investigator on the basis of RECIST version 1.1. CR=disappearance of all target lesions i.e., any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. No confirmation was required for objective response. Only participants with measurable disease at baseline were included in the analysis. The duration of one treatment cycle was 21 days; the administration of therapy in Cycle 5 did not occur until 2 weeks after surgery. The percentages have been rounded off to first decimal point.

   Time frame: At surgery (Cycle 4 Days 22-35)

6. Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Event-Free Survival (EFS) at 1, 3, and 5 Years

   Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 3 \& 5 years. EFS=time from randomization to first documentation of one of the following events: PD (before surgery) as determined by investigator with RECIST v1.1. PD=at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum during the study (nadir) with inclusion of baseline. Any evidence of contralateral disease in situ was not identified as PD; Disease recurrence (local, regional, distant, or contralateral) after surgery; Death from any cause. After treatment completion/discontinuation, follow-up data was collected every 3 months for 1 year \& then every 6 months thereafter, until disease progression/recurrence or until 5 years after randomization of last participant, whichever occurred first. Participants without an EFS event at time of analysis were censored as of the date they were last known to be alive \& event-free.

   Time frame: From Baseline to EFS event or date last known to be alive and event-free at 1, 3, and 5 years

7. Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Disease-Free Survival (DFS) at 1, 3, and 5 Years

   Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for DFS at 1, 3 and 5 years. DFS = time from first date of no disease (i.e., date of surgery) to first documentation of one of the following events: Disease recurrence (local, regional, distant, or contralateral) after surgery or death from any cause. After treatment completion/discontinuation, follow-up data was collected every 3 months for 1 year and then every 6 months thereafter, until disease progression or recurrence or until 5 years after randomization of the last participant, whichever occurred first. Participants were considered to be disease-free if they underwent surgery and no recurrence of disease was reported thereafter. Data from participants who did not have an event at analysis were censored as of the date they were last known to be alive and event-free.

   Time frame: From surgery (Cycle 4: Days 22-35) to DFS event or date last known to be alive and event-free at 1, 3, and 5 years

8. Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival (OS) at 1, 3, and 5 Years

   Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS at 1, 3 and 5 years. OS was defined as the time from randomization to death from any cause. After treatment completion/discontinuation, follow-up data was collected every 3 months for 1 year and then every 6 months thereafter, until disease progression or recurrence or until 5 years after randomization of the last participant, whichever occurred first. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive.

   Time frame: From Baseline to OS event or date last known to be alive at 1, 3, and 5 years

9. Percentage of Participants With at Least One Adverse Event (AE) During the Neoadjuvant Treatment Period

   The percentage of participants who experienced at least one AE during the neoadjuvant period is reported here. An AE is any untoward medical occurrence in a clinical investigation participant who is administered a pharmaceutical product regardless of the causal attribution. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study were also considered as adverse events. The neoadjuvant treatment period began after randomization upon receiving the first dose of any of the neoadjuvant study medications and ended before receiving the first dose of adjuvant study treatment. The duration of one treatment cycle is 21 days. The percentages have been rounded off to first decimal point.

   Time frame: Baseline up to end of Cycle 4 (1 cycle = 21 days)

10. Percentage of Participants With at Least One AE During the Adjuvant Treatment Period

    Percentage of participants who experienced at least one adverse event during the adjuvant period is reported here. An AE is any untoward medical occurrence in a clinical investigation participant who is administered a pharmaceutical product regardless of the causal attribution. An adverse event was therefore any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study were also considered as adverse events. Adjuvant treatment period began after primary surgery, upon receiving the first dose of any of the adjuvant study medications. It ended 42 days after last dose of adjuvant study treatment upon treatment completion or discontinuation. 1 Cycle=21 days. The percentages have been rounded off to first decimal point.

    Time frame: From Cycle 5 (1 cycle = 21 days) up to 42 days after the last dose in Cycle 20 Day 1 (approximately 1 year)

11. Percentage of Participants With at Least One Adverse Event During the Treatment-Free Follow-Up Period

    The percentage of participants who experienced at least one adverse event during the treatment-free follow-up period is reported here. An AE is any untoward medical occurrence in a clinical investigation participant who is administered a pharmaceutical product regardless of the causal attribution. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. The percentages have been rounded off to first decimal point.

    Time frame: From end of overall study treatment until disease progression or until 5 years after randomization of the last patient, whichever occurred first (up to 6 years)

12. Percentage of Participants Who Experienced a Primary Cardiac Event

    A primary cardiac event is defined as heart failure (New York Heart Association \[NYHA\] Class III or NYHA Class IV) and a drop in left ventricular ejection fraction (LVEF) of at least 10 ejection fraction points from baseline and to below 50%.

    Time frame: From Baseline until end of study (up to 6 years)

13. Percentage of Participants Who Experienced a Secondary Cardiac Event

    A secondary cardiac event is defined as an asymptomatic or mildly symptomatic (NYHA Class II) drop in LVEF by multiple-gated acquisition (MUGA) scan or echocardiogram confirmed by a second LVEF assessment within approximately 3 weeks showing also a documented drop. A significant LVEF drop is defined as an absolute decrease of at least 10 points below the baseline measurement and to below 50%.

    Time frame: From Baseline until end of study (up to 6 years)

14. Maximum Change From Baseline in LVEF

    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. A normal LVEF ranges from 55% to 70%, as measured by echocardiogram (preferred) or MUGA scan. The same method was used throughout the study for each participant and preferably performed and evaluated by the same assessor. Here, we report the maximum change from baseline in LVEF at any point during the study.

    Time frame: Baseline; Day 1 of Cycles 2, 4, 5, 8, 11, and 20 (1 cycle = 21 days)

15. Change From Baseline in LVEF Over Time

    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. A normal LVEF ranges from 55% to 70%, as measured by echocardiogram (preferred) or MUGA scan. The same method was used throughout the study for each participant and preferably performed and evaluated by the same assessor. Here, we report the change from baseline in LVEF over time.

    Time frame: Baseline; Day 1 of Cycles 2, 4, 5, 8, 11, and 20 (1 cycle = 21 days)

Baseline characteristics

Publications

• Shao Z, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang H, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Li J, Zhou J, Althaus B, Mao Y, Eng-Wong J. Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Mar 1;6(3):e193692. doi: 10.1001/jamaoncol.2019.3692. Epub 2020 Mar 12. PubMed 31647503 ↗

Study documents

• Study protocol · Dec 6, 2016
• Statistical analysis plan · Jul 5, 2017

Documents are hosted by the registry — open the source record to download them.