A Phase 3 interventional study of Palbociclib and Fulvestrant in Metastatic Breast Cancer, sponsored by Pfizer. Completed at 247 sites in 17 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-04-04.
Sponsored by Pfizer · Phase 3, Interventional, and Treatment
The study is a randomized, double blind, placebo controlled, Phase 3 clinical trial with the primary objective of demonstrating the superiority of palbociclib in combination with fulvestrant (Faslodex®) over fulvestrant alone in prolonging PFS in women with HR+, HER2 negative metastatic breast cancer whose disease has progressed after prior endocrine therapy. The safety between the two treatment arms will also be compared. During study treatment, pre- and perimenopausal women must be receiving therapy with the LHRH agonist goserelin (Zoladex® or generic).
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 521 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.
Drug: Palbociclib · Drug: Fulvestrant
Given until objective progression, symptomatic deterioration, unacceptable toxicity, death, or withdrawal of consent, whichever occurs first.
Drug: Placebo · Drug: Fulvestrant
Palbociclib 125 mg/day orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle.
Fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle.
Placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle.
Fulvestrant 500 mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle.
Progression-Free Survival (PFS) as Assessed by the Investigator
PFS is the time from the date of randomization to the date of the first documentation of objective progression of disease (PD)or death due to any cause in absence of documented PD. Participants lacking an evaluation of tumor response after randomization had their PFS time censored on the date of randomization with the duration of a day. Participants with documentation of PD or death after a long interval (2 or more incomplete or non-evaluable assessments) since the last tumor assessment were censored at the time of last objective assessment that did not show PD. The length of PFS was calculated as PFS time (months) =\[progression/death date(censor date) - randomization date + 1\]/30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors(RECIST v1.1) a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of existing non-target lesions or the appearance of new lesions.
Time frame: From randomization date to date of first documentation of progression or death (assessed up to 12 months)
Overall Survival (OS)-Number of Participants Who Died
OS is defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization were to have their OS times be censored at randomization. The length of OS was calculated as OS time (months) = \[death date (censor date) - randomization date + 1\]/30.4.
Time frame: From randomization until death (up to 4.5 years)
Overall Survival (OS)
OS is defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization were to have their OS times be censored at randomization. The length of OS was calculated as OS time (months) = \[death date (censor date) - randomization date + 1\]/30.4.
Time frame: From randomization until death (up to 4.5 years)
Survival Probabilities at Year 1, Year 2, and Year 3
One-, Two- or Three-year Survival Probability is defined as the probability of survival 1 year, 2 or 3 years after the date of randomization based on the Kaplan-Meier estimate. Survival time was censored to last date the participant is known to be alive.
Time frame: From randomization until death (assessed up to 36 months)
Objective Response (OR)
OR is defined as the overall complete response (CR) or partial response (PR) according to the RECIST version 1.1 Objective Response Rate (ORR) is defined as the proportion of participants with CR or PR relative to all randomized participants and randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the assessment of ORR. Per response evaluation criteria in solid tumors criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), ≥30% decrease in the sum of the longest diameter of target lesions (longest for non-nodal and short axis for nodal target lesions); Overall Response (OR) = CR + PR.
Time frame: From randomization until end of treatment (assessed up to 2 years)
Duration of Response (DR)
DR is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurs first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as \[the date response ended (ie, date of PD or death) - first CR or PR date + 1)\]/30.4. Kaplan-Meier estimate of median of the DR is provided below. No inferential statistical analysis were done for DR. The DR was only calculated for the participants with a CR or PR.
Time frame: From randomization until end of treatment (assessed up to 2 years)
Clinical Benefit Response (CBR)
CBR is defined as the overall complete response (CR), partial response (PR) , or stable disease (SD) ≥24 weeks according to the RECIST version 1.1. Clinical Benefit Response Rate (CBRR) is defined as the proportion of participants with CR, PR, or SD ≥24 weeks relative to all randomized participants and randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received antitumor treatment other than the study medication prior to reaching a CR or PR, a best response of SD ≥24 weeks, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR and a best response of SD ≥24 weeks was counted as non-responders in the assessment of CBR. Per RECIST v1.1 for target lesions and assessed by MRI: CR, disappearance of all target lesions; PR, ≥30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.
Time frame: From randomization until end of treatment (assessed up to 2 years)
Observed Plasma Trough Concentration (Ctrough) for Palbociclib
Ctrough was defined as steady-state predose concentration. Observed directly from data. For palbociclib, a steady-state trough was to be defined as a predose plasma concentration following at least 8 consecutive days of 125 mg daily dose without dosing interruption and the time window for the PK collection was to be between 22 and 26 hours after the dose (the day prior to PK collection) and no more than 1 hour post-dose on the day of PK collection.
Time frame: Cycle 1/Day 15 and Cycle 2/Day 15
Ctrough for Fulvestrant
Ctrough was defined as steady-state predose concentration. Observed directly from data. For fulvestrant, a steady-state trough was to be defined when a patient had received all prior planned doses and the sample was collected predose.
Time frame: Cycles 2/Day 1 and Cycle 3/Day 1
Ctrough for Goserelin
Ctrough was defined as steady-state predose concentration. Observed directly from data. For goserelin, a steady-state trough was to be defined when a patient had received all prior planned doses and the sample was collected predose.
Time frame: Cycles 2/ Day 1 and Cycle 3/ Day 1
Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scale Scores
The EORTC-QLQ-C30 is a 30-item questionnaire composed of five multi-item functional subscales (physical, role, emotional, cognitive , and social functioning), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global quality of life (QOL) subscale, and six single item symptom scales assessing other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and the financial impact of cancer). The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items are then converted to a 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms. A 10-point or higher change in scores from baseline is considered clinically significant.
Time frame: From Cycle 1 to 14, as of 05 December 2014.
Change From Baseline Between Treatment Comparison in EORTC QLQ-C30 Symptom Scale Scores
The EORTC-QLQ-C30 is a 30-item questionnaire composed of five multi-item functional subscales (physical, role, emotional, cognitive , and social functioning), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global quality of life (QOL) subscale, and six single item symptom scales assessing other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and the financial impact of cancer). The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items are then converted to a 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms. A 10-point or higher change in scores from baseline is considered clinically significant.
Time frame: From Cycle 1 to 14, as of 05 December 2014.
Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores
The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For functional scales, higher scores represent a better level of functioning.
Time frame: From Cycle 1 to 14, as of 05 December 2014.
Change From Baseline Between Treatment Comparison in EORTC QLQ BR23 Symptom Scale Scores
The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represent more severe symptoms.
Time frame: From Cycle 1 to 14, as of 05 December 2014.
Change From Baseline Between Treatment Comparison in EuroQoL 5D (EQ-5D)- Health Index Scores
The EuroQol-5D (version 3L) is a brief self-administered, validated instrument consisting of 2 parts. The first part consists of 5 descriptors of current health state (mobility, self care, usual activities, pain/discomfort, and anxiety/ depression); a participant is asked to rate each state on a three level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/ impairment Published weights are available that allow for the creation of a single summary score called the EQ-5D index, which basically ranges from 0 to 1 with low scores representing a higher level of dysfunction and 1 as perfect health. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time frame: From Cycle 1 to 14, as of 05 December 2014.
Change From Baseline Between Treatment Comparison in EQ-5D Visual Analog Scale (VAS) Scores Scale
The EuroQol-5D (version 3L) is a brief self-administered, validated instrument consisting of 2 parts. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time frame: From Cycle 1 to 14, as of 05 December 2014.
Time to Deterioration (TTD)
A time to event analysis was pre-specified for pain. An analysis of TTD in pain defined as time between baseline and first occurrence of increase of ≥10 points in pain. Deterioration will be defined increase in score of 10 points or greater from baseline. The Kaplan-Meier estimates of quartiles (time to deterioration) with 95% CI is mentioned below.
Time frame: Baseline, Day 1 of Cycles 2 to 4, Day 1 of every alternate cycle after that until the end of treatment, as of 05 December 2014
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)
An AE is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening; requires hospitalization; results in persistent or significant disability or in congenital anomaly/birth defect. Severity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
Time frame: From the date of randomization up to 28 calendar days (±7 days) after last dose of study intervention (up to 8.4 years).
Participants With Shifts From CTCAE Grade ≤2 at Baseline to CTCAE Grade 3 or 4 Postbaseline for Hematology Results
Number of participants with shifts from Grade ≤2 at baseline values to post-baseline values (shift to Grade 3 or 4) were reported as per NCI-CTCAE, V4.0 graded from Grade 1 to 5. Grade 1: Mild; asymptomatic/ mild symptoms; clinical/diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local/noninvasive intervention indicated. Grade 3: Severe/medically significant but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Shifts in lab parameter from Grade ≤2 at baseline to Grade 3 or 4 postbaseline (for parameters Anemia, Hemoglobin increased, Neutrophil count decreased, Platelet count decreased, and White blood cell count decreased) were reported.
Time frame: From baseline to end of treatment/withdrawal (up to 4.5 years)
Participants With Shifts From CTCAE Grade ≤2 at Baseline to CTCAE Grade 3 or 4 Postbaseline for Chemistry Results
Number of participants with shifts from Grade ≤2 at baseline values to post-baseline values (shift to Grade 3 or 4) were reported as per NCI-CTCAE, V4.0 graded from Grade 1 to 5. Grade 1: Mild; asymptomatic/ mild symptoms; clinical/diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local/noninvasive intervention indicated. Grade 3: Severe/medically significant but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Shifts in lab parameter from Grade ≤2 at baseline to Grade 3 or 4 postbaseline (for parameters ALT increased, ALP increased, AST increased, Blood bilirubin increased, Creatinine increased, Hypercalcemia, Hyperkalemia, Hypermagnesemia, Hypernatremia, Hypoalbuminemia, Hypocalcemia, Hypokalemia, Hypomagnesemia, and Hyponatremia) were reported.
Time frame: From baseline to end of treatment/withdrawal (up to 4.5 years)
The study was conducted at 144 sites in 17 countries that randomized 521 participants. Eligible participants were to have histologically or cytologically proven diagnosis of adenocarcinoma of the breast with evidence of recurrent (local or metastatic) disease.
| Milestone | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Started | 347 | 174 |
| Treated | 345 | 172 |
| Completed | 0 | 0 |
| Not completed | 347 | 174 |
| Withdrew: Adverse event | 21 | 7 |
| Withdrew: Global deterioration of health status | 9 | 6 |
| Withdrew: Randomized not treated | 2 | 2 |
| Withdrew: Death | 2 | 1 |
| Withdrew: Objective progression or relapse + progressive disease | 279 | 148 |
| Withdrew: Participant refused to continue treatment for reason other than adverse event | 10 | 3 |
| Withdrew: Withdrawal by subject | 4 | 3 |
| Withdrew: Protocol violation | 1 | 0 |
| Withdrew: Other | 19 | 4 |
PFS is the time from the date of randomization to the date of the first documentation of objective progression of disease (PD)or death due to any cause in absence of documented PD. Participants lacking an evaluation of tumor response after randomization had their PFS time censored on the date of randomization with the duration of a day. Participants with documentation of PD or death after a long interval (2 or more incomplete or non-evaluable assessments) since the last tumor assessment were censored at the time of last objective assessment that did not show PD. The length of PFS was calculated as PFS time (months) =\[progression/death date(censor date) - randomization date + 1\]/30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors(RECIST v1.1) a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5mm or unequivocal progression of existing non-target lesions or the appearance of new lesions.
| months | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Progression-Free Survival (PFS) as Assessed by the Investigator | 9.2 (7.5 to NA) | 3.8 (3.5 to 5.5) |
OS is defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization were to have their OS times be censored at randomization. The length of OS was calculated as OS time (months) = \[death date (censor date) - randomization date + 1\]/30.4.
| Participants | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Overall Survival (OS)-Number of Participants Who Died | 201 | 109 |
OS is defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization were to have their OS times be censored at randomization. The length of OS was calculated as OS time (months) = \[death date (censor date) - randomization date + 1\]/30.4.
| months | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Overall Survival (OS) | 34.9 (28.8 to 40.0) | 28.0 (23.6 to 34.6) |
One-, Two- or Three-year Survival Probability is defined as the probability of survival 1 year, 2 or 3 years after the date of randomization based on the Kaplan-Meier estimate. Survival time was censored to last date the participant is known to be alive.
| Survival Probability | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Survival Probability at Year 1 | 85.5 (81.3 to 88.9) | 84.8 (78.3 to 89.4) |
| Survival Probability at Year 2 | 65.3 (59.9 to 70.2) | 57.3 (49.2 to 64.6) |
| Survival Probability at Year 3 | 49.6 (44.0 to 54.9) | 40.8 (32.9 to 48.5) |
OR is defined as the overall complete response (CR) or partial response (PR) according to the RECIST version 1.1 Objective Response Rate (ORR) is defined as the proportion of participants with CR or PR relative to all randomized participants and randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the assessment of ORR. Per response evaluation criteria in solid tumors criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), ≥30% decrease in the sum of the longest diameter of target lesions (longest for non-nodal and short axis for nodal target lesions); Overall Response (OR) = CR + PR.
| percentage of participants | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Objective Response (OR) | 21.0 (16.9 to 25.7) | 8.6 (4.9 to 13.8) |
DR is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurs first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as \[the date response ended (ie, date of PD or death) - first CR or PR date + 1)\]/30.4. Kaplan-Meier estimate of median of the DR is provided below. No inferential statistical analysis were done for DR. The DR was only calculated for the participants with a CR or PR.
| Months | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Duration of Response (DR) | 10.4 (8.3 to NA) | 9.0 (5.6 to NA) |
CBR is defined as the overall complete response (CR), partial response (PR) , or stable disease (SD) ≥24 weeks according to the RECIST version 1.1. Clinical Benefit Response Rate (CBRR) is defined as the proportion of participants with CR, PR, or SD ≥24 weeks relative to all randomized participants and randomized participants with measurable disease at baseline. Participants who do not have on-study radiographic tumor re-evaluation, who received antitumor treatment other than the study medication prior to reaching a CR or PR, a best response of SD ≥24 weeks, or who died, progressed, or dropped out for any reason prior to reaching a CR or PR and a best response of SD ≥24 weeks was counted as non-responders in the assessment of CBR. Per RECIST v1.1 for target lesions and assessed by MRI: CR, disappearance of all target lesions; PR, ≥30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.
| percentage of participants | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Clinical Benefit Response (CBR) | 66.3 (61.0 to 71.2) | 39.7 (32.3 to 47.3) |
Ctrough was defined as steady-state predose concentration. Observed directly from data. For palbociclib, a steady-state trough was to be defined as a predose plasma concentration following at least 8 consecutive days of 125 mg daily dose without dosing interruption and the time window for the PK collection was to be between 22 and 26 hours after the dose (the day prior to PK collection) and no more than 1 hour post-dose on the day of PK collection.
| nanograms per milliliter (ng/mL) | Palbociclib + Fulvestrant |
|---|---|
| Cycle 1/Day 15 | 70.70 ± 44 |
| Cycle 2/Day 15 | 75.29 ± 44 |
Ctrough was defined as steady-state predose concentration. Observed directly from data. For fulvestrant, a steady-state trough was to be defined when a patient had received all prior planned doses and the sample was collected predose.
| ng/mL | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Cycle 2/Day 1 | 11.75 ± 41 | 9.31 ± 52 |
| Cycle 3/Day 1 | 9.90 ± 42 | 7.60 ± 72 |
Ctrough was defined as steady-state predose concentration. Observed directly from data. For goserelin, a steady-state trough was to be defined when a patient had received all prior planned doses and the sample was collected predose.
| picograms per milliliter (pg/mL) | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Cycle 2/Day 1 | 295.1 ± 153 | 302.5 ± 74 |
| Cycle 3/Day 1 | 344.8 ± 64 | 288.5 ± 40 |
The EORTC-QLQ-C30 is a 30-item questionnaire composed of five multi-item functional subscales (physical, role, emotional, cognitive , and social functioning), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global quality of life (QOL) subscale, and six single item symptom scales assessing other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and the financial impact of cancer). The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items are then converted to a 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms. A 10-point or higher change in scores from baseline is considered clinically significant.
| Units on a scale | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Global health status / QoL | -0.9 ± 64.5 | -4.0 ± 26.25 |
| Physical functioning | -0.7 ± 22.76 | -1.7 ± 21.24 |
| Role functioning | -1.8 ± 30.70 | -3.7 ± 28.04 |
| Emotional functioning | 2.7 ± 25.97 | -1.9 ± 21.19 |
| Cognitive functioning | -1.7 ± 20.97 | -2.9 ± 20.22 |
| Social functioning | -0.5 ± 32.07 | -0.6 ± 32.27 |
The EORTC-QLQ-C30 is a 30-item questionnaire composed of five multi-item functional subscales (physical, role, emotional, cognitive , and social functioning), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global quality of life (QOL) subscale, and six single item symptom scales assessing other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and the financial impact of cancer). The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items are then converted to a 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms. A 10-point or higher change in scores from baseline is considered clinically significant.
| Units on a scale | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Fatigue | 1.8 ± 26.12 | 3.3 ± 24.82 |
| Nausea and vomiting | 1.7 ± 26.06 | 4.2 ± 19.71 |
| Pain | -3.3 ± 29.02 | 2.0 ± 30.04 |
| Dyspnoea | 2.8 ± 30.32 | 3.3 ± 24.98 |
| Insomnia | -2.4 ± 29.81 | -0.4 ± 29.30 |
| Appetite loss | 1.1 ± 36.43 | 1.7 ± 29.61 |
| Constipation | 3.5 ± 32.05 | 2.8 ± 26.05 |
| Diarrhoea | 1.9 ± 18.97 | 2.4 ± 26.12 |
| Financial difficulties | -3.7 ± 28.87 | -4.0 ± 26.30 |
The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For functional scales, higher scores represent a better level of functioning.
| Units on a scale | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Body image | 1.9 ± 28.07 | -0.3 ± 20.33 |
| Sexual functioning | -1.1 ± 16.08 | -0.4 ± 18.23 |
| Sexual enjoyment | -5.2 ± 20.80 | -6.6 ± 25.49 |
| Future perspective | 8.1 ± 30.63 | 4.5 ± 30.00 |
The EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and four symptom scales (systemic side effects, breast symptoms, arm symptoms, upset by hair loss). QLQ-BR23 questionnaire employs 4-point scales with responses from 'not at all' to 'very much'. All scores are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represent more severe symptoms.
| Units on a scale | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Systemic therapy side effects | 3.8 ± 15.19 | 3.4 ± 14.31 |
| Breast symptoms | -2.2 ± 21.32 | -1.3 ± 17.49 |
| Arm symptoms | -2.2 ± 20.59 | -2.0 ± 20.08 |
| Upset by hair loss | 2.9 ± 30.19 | -6.0 ± 20.91 |
The EuroQol-5D (version 3L) is a brief self-administered, validated instrument consisting of 2 parts. The first part consists of 5 descriptors of current health state (mobility, self care, usual activities, pain/discomfort, and anxiety/ depression); a participant is asked to rate each state on a three level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/ impairment Published weights are available that allow for the creation of a single summary score called the EQ-5D index, which basically ranges from 0 to 1 with low scores representing a higher level of dysfunction and 1 as perfect health. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).
| Units on a scale | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Change From Baseline Between Treatment Comparison in EuroQoL 5D (EQ-5D)- Health Index Scores | 0.006 (-0.01 to 0.03) | -0.031 (-0.06 to 0.00) |
The EuroQol-5D (version 3L) is a brief self-administered, validated instrument consisting of 2 parts. The second part consists of the EQ-5D general health status as measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).
| Units on a scale | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Change From Baseline Between Treatment Comparison in EQ-5D Visual Analog Scale (VAS) Scores Scale | -1.8 ± 19.00 | -2.6 ± 23.09 |
A time to event analysis was pre-specified for pain. An analysis of TTD in pain defined as time between baseline and first occurrence of increase of ≥10 points in pain. Deterioration will be defined increase in score of 10 points or greater from baseline. The Kaplan-Meier estimates of quartiles (time to deterioration) with 95% CI is mentioned below.
| Months | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| 25% quartile | 1.9 (1.2 to 2.2) | 1.0 (1.0 to 1.9) |
| 50% quartile | 8.0 (5.6 to NA) | 2.8 (2.3 to 5.4) |
An AE is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening; requires hospitalization; results in persistent or significant disability or in congenital anomaly/birth defect. Severity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
| percentage of participants | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| With AEs | 98.8 | 93.6 |
| With SAEs | 22.6 | 19.2 |
| With Grade 3 or 4 AEs | 80.6 | 26.7 |
| With Grade 5 AEs | 2.3 | 1.7 |
| Discontinued palbociclib/placebo due to AEs | 7.5 | 4.7 |
Number of participants with shifts from Grade ≤2 at baseline values to post-baseline values (shift to Grade 3 or 4) were reported as per NCI-CTCAE, V4.0 graded from Grade 1 to 5. Grade 1: Mild; asymptomatic/ mild symptoms; clinical/diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local/noninvasive intervention indicated. Grade 3: Severe/medically significant but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Shifts in lab parameter from Grade ≤2 at baseline to Grade 3 or 4 postbaseline (for parameters Anemia, Hemoglobin increased, Neutrophil count decreased, Platelet count decreased, and White blood cell count decreased) were reported.
| Participants | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Anemia | 16 | 3 |
| Hemoglobin increased | 1 | 0 |
| Neutrophil count decreased | 239 | 1 |
| Platelet count decreased | 10 | 0 |
| White blood cell count decreased | 167 | 0 |
Number of participants with shifts from Grade ≤2 at baseline values to post-baseline values (shift to Grade 3 or 4) were reported as per NCI-CTCAE, V4.0 graded from Grade 1 to 5. Grade 1: Mild; asymptomatic/ mild symptoms; clinical/diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local/noninvasive intervention indicated. Grade 3: Severe/medically significant but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Shifts in lab parameter from Grade ≤2 at baseline to Grade 3 or 4 postbaseline (for parameters ALT increased, ALP increased, AST increased, Blood bilirubin increased, Creatinine increased, Hypercalcemia, Hyperkalemia, Hypermagnesemia, Hypernatremia, Hypoalbuminemia, Hypocalcemia, Hypokalemia, Hypomagnesemia, and Hyponatremia) were reported.
| Participants | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| ALT increased | 10 | 1 |
| ALP increased | 2 | 2 |
| AST increased | 13 | 7 |
| Blood bilirubin increased | 2 | 3 |
| Creatinine increased | 5 | 0 |
| Hypercalcemia | 1 | 0 |
| Hyperkalemia | 2 | 2 |
| Hypermagnesemia | 7 | 2 |
| Hypernatremia | 0 | 1 |
| Hypoalbuminemia | 0 | 1 |
| Hypocalcemia | 2 | 2 |
| Hypokalemia | 0 | 0 |
| Hypomagnesemia | 0 | 0 |
| Hyponatremia | 12 | 4 |
Collected over From the date of randomization up to 28 calendar days (±7 days) after last dose of study intervention (up to 8.4 years).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Palbociclib + Fulvestrant | 201/347 (57.9%) | 78/345 (22.6%) | 341/345 (98.8%) |
| Placebo + Fulvestrant | 109/174 (62.6%) | 33/172 (19.2%) | 161/172 (93.6%) |
| Event | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 2/345 | 3/172 |
| PyrexiaGeneral disorders | 5/345 | 1/172 |
| AscitesGastrointestinal disorders | 0/345 | 2/172 |
| PneumoniaInfections and infestations | 3/345 | 2/172 |
| Pathological fractureMusculoskeletal and connective tissue disorders | 0/345 | 2/172 |
| NeutropeniaBlood and lymphatic system disorders | 4/345 | 0/172 |
| Disease progressionGeneral disorders | 4/345 | 0/172 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 4/345 | 0/172 |
| Febrile neutropeniaBlood and lymphatic system disorders | 3/345 | 0/172 |
| Deep vein thrombosisVascular disorders | 3/345 | 0/172 |
| Event | Palbociclib + Fulvestrant | Placebo + Fulvestrant |
|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 231/345 | 4/172 |
| FatigueGeneral disorders | 151/345 | 56/172 |
| NauseaGastrointestinal disorders | 126/345 | 51/172 |
| LeukopeniaBlood and lymphatic system disorders | 113/345 | 2/172 |
| AnaemiaBlood and lymphatic system disorders | 108/345 | 23/172 |
| White blood cell count decreasedInvestigations | 107/345 | 7/172 |
| HeadacheNervous system disorders | 102/345 | 38/172 |
| DiarrhoeaGastrointestinal disorders | 95/345 | 35/172 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 90/345 | 42/172 |
| Neutrophil count decreasedInvestigations | 84/345 | 2/172 |
The intent-to-treat (ITT) population or full analysis set included all participants who were randomized, with study intervention assignment designated according to initial randomization, regardless of whether participants received study intervention or received a different drug from that to which they were randomized.
| Age, Continuous(Years) | Palbociclib + Fulvestrant | Placebo + Fulvestrant | Total |
|---|---|---|---|
| Mean | 56.9 ± 11.7 | 56.8 ± 10.4 | 56.9 ± 11.3 |
| Sex: Female, Male(Participants) | Palbociclib + Fulvestrant | Placebo + Fulvestrant | Total |
|---|---|---|---|
| Female | 347 | 174 | 521 |
| Male | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Palbociclib + Fulvestrant | Placebo + Fulvestrant | Total |
|---|---|---|---|
| Hispanic or Latino | 17 | 11 | 28 |
| Not Hispanic or Latino | 329 | 161 | 490 |
| Unknown or Not Reported | 1 | 2 | 3 |
| Menopausal Status(Participants) | Palbociclib + Fulvestrant | Placebo + Fulvestrant | Total |
|---|---|---|---|
| Postmenopausal | 275 | 138 | 413 |
| Pre/Perimenopausal | 72 | 36 | 108 |
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Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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