Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Palbociclib (PD-0332991) Combined With Fulvestrant In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After Endocrine Failure (PALOMA-3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01942135
Recruitment Status : Active, not recruiting
First Posted : September 13, 2013
Results First Posted : May 23, 2016
Last Update Posted : November 27, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Metastatic Breast Cancer
Interventions Drug: Palbociclib
Drug: Fulvestrant
Drug: Placebo
Enrollment 521
Recruitment Details 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.
Pre-assignment Details The study consisted of a screening visit within 28 days before randomization, an active treatment phase, divided in cycles of 28 days each, and a post-treatment follow-up period during which survival and new anti-cancer therapy information was collected every 3 months for the first 9 months, then every 6 months from the last dose of study drug.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase. Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Period Title: Overall Study
Started 347 174
Completed 0 0
Not Completed 347 174
Reason Not Completed
Adverse Event             9             3
Global deterioration of health status             8             3
Randomized Not Treated             2             2
Death             0             1
ObjectiveProgression+Progressive Disease             85             87
Participant Refused toContinue Treatment             1             1
Withdrawal by Subject             4             2
Ongoing at date of cut-off (05 Dec 2014)             238             75
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant Total
Hide Arm/Group Description Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase. Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase. Total of all reporting groups
Overall Number of Baseline Participants 347 174 521
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 347 participants 174 participants 521 participants
56.9  (11.7) 56.8  (10.4) 56.9  (11.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 347 participants 174 participants 521 participants
Female
347
 100.0%
174
 100.0%
521
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Progression-Free Survival (PFS) as Assessed by the Investigator
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population or full analysis set included all participants who were randomized, with study medication, regardless of whether participants received the study medication or received a different drug from that to which they were randomized.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 347 174
Median (95% Confidence Interval)
Unit of Measure: Months
9.2 [1] 
(7.5 to NA)
3.8
(3.5 to 5.5)
[1]
This parameter is not estimable when the Kaplan Meier-based curve representing the upper confidence limits for survival function lies above 50%, which suggested that this arm was performing well in terms of PFS prolongation at the data cutoff date.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments The primary hypothesis to be tested was H0: λ≥1 versus. HA: λ<1, where λ was the palbociclib plus fulvestrant: placebo plus fulvestrant hazard ratio (HR). A HR less than 1 indicates a reduction in hazard rate in favor of Palbociclib + Fulvestrant. The study was planned to have 90% power and control the type-I error rate at 0.025.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.000001
Comments The overall Type-I error rate was persevered at 1-sided 0.025 level for the analysis of the primary endpoint PFS by the Haybittle-Peto efficacy boundary. The priori threshold for statistical significance at the interim analysis was 0.00135.
Method Stratified Log Rank Test (1-sided)
Comments The log rank test stratified by sensitivity to prior hormonal therapy and the presence of visceral metastases based on the randomization information.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.422
Confidence Interval (2-Sided) 95%
0.318 to 0.560
Estimation Comments Assuming proportional hazards, a hazard ratio less than 1 indicates a reduction in hazard rate in favor of the palbociclib plus fulvestrant arm.
2.Secondary Outcome
Title Overall Survival (OS) - Number of Participants Who Died
Hide Description 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. No inferential statistical analysis were done because of the immaturity of the OS data.
Time Frame From randomization until death (up to approximately 36 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population or full analysis set included all participants who were randomized, with study medication, regardless of whether participants received the study medication or received a different drug from that to which they were randomized.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 347 174
Measure Type: Number
Unit of Measure: deaths
19 9
3.Secondary Outcome
Title Objective Response (OR)
Hide Description 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 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population or full analysis set included all participants who were randomized, with study medication, regardless of whether participants received the study medication or received a different drug from that to which they were randomized. Randomized participants with measurable disease at baseline was also included.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 347 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
10.4
(7.4 to 14.1)
6.3
(3.2 to 11.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments The exact test is testing the null hypothesis that the odds ratio of objective response rate is less than or equal to 1 vs. the alternative hypothesis that the odds ratio of objective response rate is greater than 1. An Odds Ratio >1 means better response in favor of palbociclib plus fulvestrant arm.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0791
Comments The p-value was not adjusted for multiple comparisons. The priori threshold for statistical significance is 1-sided, alpha=0.025.
Method Exact test (1-sided)
Comments The 1-sided p-value is from the stratified exact test.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.725
Confidence Interval (2-Sided) 95%
0.835 to 3.896
Estimation Comments An Odds Ratio >1 means better response in favor of the palbociclib plus fulvestrant arm.
4.Secondary Outcome
Title Duration of Response (DR)
Hide Description 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 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population or full analysis set included all participants who were randomized, with study medication, regardless of whether participants received the study medication or received a different drug from that to which they were randomized.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 347 174
Median (95% Confidence Interval)
Unit of Measure: Months
9.3 [1] 
(4.0 to NA)
5.7
(3.7 to 5.7)
[1]
Due to less follow-up time and insufficient number of participants having Duration Response.
5.Secondary Outcome
Title Clinical Benefit Response (CBR)
Hide Description 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 12 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population or full analysis set included all participants who were randomized, with study medication, regardless of whether participants received the study medication or received a different drug from that to which they were randomized. Randomized participants with measurable disease at baseline was also included.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 347 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
34.0
(29.0 to 39.3)
19.0
(13.4 to 25.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments The exact test is testing the null hypothesis that the odds ratio of objective response rate is less than or equal to 1 vs. the alternative hypothesis that the odds ratio of objective response rate is greater than 1. An Odds Ratio >1 means better response in favor of palbociclib plus fulvestrant arm.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments The p-value was not adjusted for multiple comparisons. The priori threshold for statistical significance is 1-sided, alpha=0.025.
Method Exact test (1-sided)
Comments The 1-sided p-value is from the stratified exact test.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.189
Confidence Interval (2-Sided) 95%
1.391 to 3.523
Estimation Comments An odds ratio > 1 means better clinical benefit response in favor of palbociclib plus fulvestrant arm.
6.Secondary Outcome
Title Survival Probabilities at Months 12, 24 and 36
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population or full analysis set included all participants who were randomized, with study medication, regardless of whether participants received the study medication or received a different drug from that to which they were randomized.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 347 174
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Survival Probability at Month 12
89.3
(78.1 to 95.0)
89.3
(77.8 to 95.0)
Survival Probability at Month 24
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Survival Probability at Month 36
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Due to less follow-up time and insufficient number of participants with events.
7.Secondary Outcome
Title Observed Plasma Trough Concentration (Ctrough) for Palbociclib
Hide Description Ctrough for palbociclib (if applicable). The method of dispersion applied here is "percent coefficient of variation" (%CV).
Time Frame Cycle 1/Day 15 and Cycle 2/Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had PK blood samples collected for palbociclib and had at least one measured plasma drug concentration.
Arm/Group Title Palbociclib + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 325
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1/Day 15 (N= 165)
70.70
(44%)
Cycle 2/Day 15 (N= 160)
75.29
(44%)
8.Secondary Outcome
Title Ctrough for Fulvestrant
Hide Description Ctrough for Fulvestrant (if applicable). The method of dispersion applied here is "percent coefficient of variation" (%CV).
Time Frame Cycles 2/Day 1 and Cycle 3/Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had PK blood samples collected for palbociclib and had at least one measured plasma drug concentration.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 64 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 2/Day 1 (N= 35, 19)
11.75
(41%)
9.31
(52%)
Cycle 3/Day 1 (N= 29, 14)
9.90
(42%)
7.60
(72%)
9.Secondary Outcome
Title Ctrough for Goserelin
Hide Description Cmin for goserelin (if applicable). The method of dispersion applied here is "percent coefficient of variation" (%CV).
Time Frame Cycles 2/ Day 1 and Cycle 3/ Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who had PK blood samples collected for palbociclib and had at least one measured plasma drug concentration.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 16 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: pg/mL
Cycle 2/Day 1 (N= 9, 5)
295.1
(153%)
302.5
(74%)
Cycle 3/Day 1 (N= 7, 3)
344.8
(64%)
288.5
(40%)
10.Secondary Outcome
Title 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
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The PRO –evaluable population is defined as a subset of ITT participants, who have completed a baseline and at least one post –baseline PRO assessment prior to end of study treatment. Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 335 166
Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
Global health status / QoL
-0.9
(-2.5 to 0.7)
-4.0
(-6.3 to -1.7)
Physical functioning
-0.7
(-2.1 to 0.7)
-1.7
(-3.7 to 0.2)
Role functioning
-1.8
(-3.7 to 0.1)
-3.7
(-6.5 to -0.9)
Emotional functioning
2.7
(1.1 to 4.3)
-1.9
(-4.2 to 0.5)
Cognitive functioning
-1.7
(-3.1 to -0.2)
-2.9
(-5.0 to -0.7)
Social functioning
-0.5
(-2.5 to 1.5)
-0.6
(-3.4 to 2.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for Global health status/ QoL
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0313
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.1
Confidence Interval (2-Sided) 95%
0.3 to 6.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for physical functioning
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4000
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-1.4 to 3.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for role functioning
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2615
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.9
Confidence Interval (2-Sided) 95%
-1.5 to 5.3
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for emotional functioning
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.6
Confidence Interval (2-Sided) 95%
1.7 to 7.4
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for cognitive functioning
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3650
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-1.4 to 3.8
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for social functioning
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9615
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-3.4 to 3.5
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline Between Treatment Comparison in EORTC QLQ-C30 Symptom Scale Scores
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The PRO –evaluable population is defined as a subset of ITT participants, who have completed a baseline and at least one post –baseline PRO assessment prior to end of study treatment. Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 335 166
Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
Fatigue
1.8
(0.1 to 3.5)
3.3
(0.9 to 5.8)
Nausea and vomiting
1.7
(0.4 to 3.0)
4.2
(2.3 to 6.1)
Pain
-3.3
(-5.1 to -1.5)
2.0
(-0.6 to 4.6)
Dyspnoea
2.8
(1.0 to 4.7)
3.3
(0.6 to 6.0)
Insomnia
-2.4
(-4.4 to -0.4)
-0.4
(-3.3 to 2.5)
Appetite loss
1.1
(-0.8 to 3.1)
1.7
(-1.1 to 4.6)
Constipation
3.5
(1.7 to 5.3)
2.8
(0.1 to 5.4)
Diarrhoea
1.9
(0.6 to 3.1)
2.4
(0.5 to 4.3)
Financial difficulties
-3.7
(-5.6 to -1.9)
-4.0
(-6.7 to -1.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for fatigue
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3200
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.5
Confidence Interval (2-Sided) 95%
-4.5 to 1.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for nausea and vomiting
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0369
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-4.8 to -0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for pain
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.3
Confidence Interval (2-Sided) 95%
-8.5 to -2.1
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for dyspnoea
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7699
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-3.7 to 2.8
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for insomnia
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2721
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-5.5 to 1.6
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for appetite loss
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7334
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-4.1 to 2.9
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for constipation
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6491
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-2.5 to 3.9
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for diarrhoea
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6293
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-2.8 to 1.7
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for financial difficulties
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8812
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-3.1 to 3.6
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline Between Treatment Comparison in European Organization for Research and Treatment of Cancer Breast Cancer Module (EORTC QLQ BR23) Functional Scale Scores
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The PRO –evaluable population is defined as a subset of ITT participants, who have completed a baseline and at least one post –baseline PRO assessment prior to end of study treatment. Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 335 166
Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
Body image
1.9
(0.2 to 3.6)
-0.3
(-2.8 to 2.1)
Sexual functioning
-1.1
(-2.5 to 0.2)
-0.4
(-2.3 to 1.5)
Sexual enjoyment
-5.2
(-8.3 to -2.1)
-6.6
(-11.6 to -1.7)
Future perspective
8.1
(5.8 to 10.4)
4.5
(1.2 to 7.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for body image
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1386
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.3
Confidence Interval (2-Sided) 95%
-0.7 to 5.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for sexual functioning
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5235
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-3.1 to 1.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for sexual enjoyment
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6271
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-4.4 to 7.3
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for future perspective
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0845
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.6
Confidence Interval (2-Sided) 95%
-0.5 to 7.6
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline Between Treatment Comparison in EORTC QLQ BR23 Symptom Scale Scores
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The PRO –evaluable population is defined as a subset of ITT participants, who have completed a baseline and at least one post –baseline PRO assessment prior to end of study treatment. Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 335 166
Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
Systemic therapy side effects
3.8
(2.6 to 4.9)
3.4
(1.8 to 5.0)
Breast symptoms
-2.2
(-3.2 to -1.3)
-1.3
(-2.7 to 0.0)
Arm symptoms
-2.2
(-3.6 to -0.9)
-2.0
(-4.0 to -0.1)
Upset by hair loss
2.9
(-1.7 to 7.4)
-6.0
(-12.3 to 0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for systemic therapy side effects
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7273
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.6 to 2.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for breast symptoms
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2671
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.6 to 0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for arm symptoms
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8750
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-2.6 to 2.2
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Statistical significance for palbociclib plus fulvestrant vs placebo plus fulvestrant for upset by hair loss
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0255
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 8.9
Confidence Interval (2-Sided) 95%
1.1 to 16.6
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline Between Treatment Comparison in EuroQoL 5D (EQ-5D)- Health Index Scores
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The PRO –evaluable population is defined as a subset of ITT participants, who have completed a baseline and at least one post –baseline PRO assessment prior to end of study treatment. Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 335 166
Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
0.006
(-0.01 to 0.03)
-0.031
(-0.06 to 0.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0308
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.037
Confidence Interval (2-Sided) 95%
0.00 to 0.07
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline Between Treatment Comparison in EQ-5D Visual Analog Scale (VAS) Scores Scale
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The PRO –evaluable population is defined as a subset of ITT participants, who have completed a baseline and at least one post –baseline PRO assessment prior to end of study treatment. Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 335 166
Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
-1.8
(-3.3 to -0.3)
-2.6
(-4.8 to -0.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5523
Comments The priori threshold for statistical significance is 2-sided alpha=0.05. The p-value was not adjusted for multiple comparisons.
Method Mixed Model Analysis (2-sided)
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-1.9 to 3.5
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Time to Deterioration (TTD)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The PRO –evaluable population is defined as a subset of ITT participants, who have completed a baseline and at least one post –baseline PRO assessment prior to end of study treatment.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 335 166
Median (95% Confidence Interval)
Unit of Measure: Months
25% quartile
1.9
(1.2 to 2.2)
1.0
(1.0 to 1.9)
50% quartile
8.0 [1] 
(5.6 to NA)
2.8
(2.3 to 5.4)
[1]
Due to less follow-up time and insufficient number of participants with events.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib + Fulvestrant, Placebo + Fulvestrant
Comments Treatment with palbociclib plus fulvestrant significantly delayed TTD in pain symptom compared with placebo plus fulvestrant for unstratified analysis.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The priori threshold for statistical significance is 1-sided alpha=0.025. The p-value was not adjusted for multiple comparisons.
Method Unstratified log-rank test (1-sided)
Comments 1-sided p-value from the unstratified log-rank test.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.642
Confidence Interval (2-Sided) 95%
0.487 to 0.846
Estimation Comments Assuming proportional hazards, a hazard ratio less than 1 indicates a reduction in hazard rate in favor of the palbociclib plus fulvestrant arm.
17.Secondary Outcome
Title Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)
Hide Description 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 signing of the informed consent until 28 days after the last dose of study medication up to 14 months
Hide Outcome Measure Data
Hide Analysis Population Description
The as-treated (AT) population or safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description:
Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
Overall Number of Participants Analyzed 345 172
Measure Type: Number
Unit of Measure: Percentage of Participants
With AEs 97.7 89.0
With SAEs 9.6 14.0
With Grade 3 or 4 AEs 70.1 18.0
With Grade 5 AEs 0.9 1.2
Discontinued palbociclib/placebo due to AEs 3.8 4.1
Time Frame From the date of randomization up to 28 calendar days (±7 days) after last dose of study medication up to 14 months.
Adverse Event Reporting Description The safety analysis set included participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.
 
Arm/Group Title Palbociclib + Fulvestrant Placebo + Fulvestrant
Hide Arm/Group Description Participants were administered an initial dose of 125 mg per day orally continuously for 3 weeks followed by 1 week off that can be reduced to 100 mg or 75 mg in case of toxicity; repeated at each subsequent cycle and fulvestrant 500 mg intramuscularly on days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase. Participants were administered placebo orally continuously dosed for 3 weeks followed by 1 week off; repeated at each subsequent cycle and Fulvestrant 500 mg intramuscularly on Days 1 and 15 of cycle 1 and then every 28 days. Pre- and perimenopausal women received goserelin at least 4 weeks before study treatment start and continued receiving concurrent ovarian function suppression with goserelin administered subcutaneously every 28 days during the active treatment phase.
All-Cause Mortality
Palbociclib + Fulvestrant Placebo + Fulvestrant
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Palbociclib + Fulvestrant Placebo + Fulvestrant
Affected / at Risk (%) Affected / at Risk (%)
Total   33/345 (9.57%)   24/172 (13.95%) 
Blood and lymphatic system disorders     
Disseminated intravascular coagulation * 1  1/345 (0.29%)  0/172 (0.00%) 
Febrile neutropenia * 1  1/345 (0.29%)  1/172 (0.58%) 
Neutropenia * 1  1/345 (0.29%)  0/172 (0.00%) 
Cardiac disorders     
Atrial fibrillation * 1  1/345 (0.29%)  0/172 (0.00%) 
Pericarditis * 1  1/345 (0.29%)  0/172 (0.00%) 
Endocrine disorders     
Hyperthyroidism * 1  1/345 (0.29%)  0/172 (0.00%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/345 (0.29%)  0/172 (0.00%) 
Ascites * 1  0/345 (0.00%)  2/172 (1.16%) 
Duodenogastric reflux * 1  1/345 (0.29%)  0/172 (0.00%) 
Intestinal obstruction * 1  1/345 (0.29%)  0/172 (0.00%) 
Nausea * 1  0/345 (0.00%)  1/172 (0.58%) 
Pancreatitis * 1  0/345 (0.00%)  1/172 (0.58%) 
Vomiting * 1  1/345 (0.29%)  1/172 (0.58%) 
General disorders     
Chest pain * 1  0/345 (0.00%)  1/172 (0.58%) 
Device occlusion * 1  1/345 (0.29%)  0/172 (0.00%) 
Disease progression * 1  2/345 (0.58%)  0/172 (0.00%) 
General physical health deterioration * 1  1/345 (0.29%)  0/172 (0.00%) 
Non-cardiac chest pain * 1  0/345 (0.00%)  1/172 (0.58%) 
Oedema peripheral * 1  1/345 (0.29%)  1/172 (0.58%) 
Pain * 1  1/345 (0.29%)  0/172 (0.00%) 
Pyrexia * 1  3/345 (0.87%)  1/172 (0.58%) 
Hepatobiliary disorders     
Cholecystitis * 1  0/345 (0.00%)  1/172 (0.58%) 
Cholelithiasis * 1  1/345 (0.29%)  0/172 (0.00%) 
Hepatic failure * 1  1/345 (0.29%)  0/172 (0.00%) 
Infections and infestations     
Bacteraemia * 1  1/345 (0.29%)  0/172 (0.00%) 
Cellulitis * 1  1/345 (0.29%)  0/172 (0.00%) 
Erysipelas * 1  1/345 (0.29%)  0/172 (0.00%) 
Gastrointestinal infection * 1  0/345 (0.00%)  1/172 (0.58%) 
Otitis media acute * 1  1/345 (0.29%)  0/172 (0.00%) 
Pharyngitis * 1  1/345 (0.29%)  0/172 (0.00%) 
Pneumonia * 1  1/345 (0.29%)  2/172 (1.16%) 
Pyelonephritis * 1  0/345 (0.00%)  1/172 (0.58%) 
Upper respiratory tract infection * 1  1/345 (0.29%)  0/172 (0.00%) 
Urinary tract infection * 1  1/345 (0.29%)  0/172 (0.00%) 
Injury, poisoning and procedural complications     
Femur fracture * 1  0/345 (0.00%)  1/172 (0.58%) 
Fracture * 1  0/345 (0.00%)  1/172 (0.58%) 
Humerus fracture * 1  0/345 (0.00%)  1/172 (0.58%) 
Road traffic accident * 1  0/345 (0.00%)  1/172 (0.58%) 
Investigations     
Alanine aminotransferase increased * 1  1/345 (0.29%)  0/172 (0.00%) 
Electrocardiogram QT prolonged * 1  1/345 (0.29%)  0/172 (0.00%) 
Neutrophil count * 1  1/345 (0.29%)  0/172 (0.00%) 
Troponin increased * 1  1/345 (0.29%)  0/172 (0.00%) 
Metabolism and nutrition disorders     
Dehydration * 1  1/345 (0.29%)  0/172 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/345 (0.29%)  2/172 (1.16%) 
Osteonecrosis of jaw * 1  0/345 (0.00%)  1/172 (0.58%) 
Pain in extremity * 1  1/345 (0.29%)  0/172 (0.00%) 
Pathological fracture * 1  0/345 (0.00%)  1/172 (0.58%) 
Nervous system disorders     
Aphasia * 1  0/345 (0.00%)  1/172 (0.58%) 
Cerebral haemorrhage * 1  0/345 (0.00%)  1/172 (0.58%) 
Cerebrovascular accident * 1  0/345 (0.00%)  1/172 (0.58%) 
Dysarthria * 1  0/345 (0.00%)  1/172 (0.58%) 
Facial paresis * 1  0/345 (0.00%)  1/172 (0.58%) 
Migraine * 1  1/345 (0.29%)  0/172 (0.00%) 
Sedation * 1  1/345 (0.29%)  0/172 (0.00%) 
Somnolence * 1  1/345 (0.29%)  0/172 (0.00%) 
Psychiatric disorders     
Depression * 1  1/345 (0.29%)  0/172 (0.00%) 
Psychotic disorder * 1  1/345 (0.29%)  0/172 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome * 1  0/345 (0.00%)  1/172 (0.58%) 
Chronic obstructive pulmonary disease * 1  1/345 (0.29%)  1/172 (0.58%) 
Dyspnoea * 1  1/345 (0.29%)  1/172 (0.58%) 
Pleural effusion * 1  1/345 (0.29%)  3/172 (1.74%) 
Pulmonary embolism * 1  3/345 (0.87%)  0/172 (0.00%) 
Pulmonary hypertension * 1  0/345 (0.00%)  1/172 (0.58%) 
Skin and subcutaneous tissue disorders     
Rash maculo-papular * 1  1/345 (0.29%)  0/172 (0.00%) 
Vascular disorders     
Deep vein thrombosis * 1  1/345 (0.29%)  0/172 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Palbociclib + Fulvestrant Placebo + Fulvestrant
Affected / at Risk (%) Affected / at Risk (%)
Total   333/345 (96.52%)   147/172 (85.47%) 
Blood and lymphatic system disorders     
Anaemia * 1  88/345 (25.51%)  17/172 (9.88%) 
Leukopenia * 1  70/345 (20.29%)  2/172 (1.16%) 
Neutropenia * 1  212/345 (61.45%)  3/172 (1.74%) 
Thrombocytopenia * 1  40/345 (11.59%)  0/172 (0.00%) 
Gastrointestinal disorders     
Abdominal pain * 1  21/345 (6.09%)  9/172 (5.23%) 
Abdominal pain upper * 1  12/345 (3.48%)  11/172 (6.40%) 
Constipation * 1  58/345 (16.81%)  24/172 (13.95%) 
Diarrhoea * 1  66/345 (19.13%)  30/172 (17.44%) 
Dry mouth * 1  22/345 (6.38%)  14/172 (8.14%) 
Dyspepsia * 1  25/345 (7.25%)  7/172 (4.07%) 
Nausea * 1  100/345 (28.99%)  44/172 (25.58%) 
Stomatitis * 1  40/345 (11.59%)  4/172 (2.33%) 
Vomiting * 1  50/345 (14.49%)  20/172 (11.63%) 
General disorders     
Asthenia * 1  23/345 (6.67%)  8/172 (4.65%) 
Chest pain * 1  6/345 (1.74%)  9/172 (5.23%) 
Fatigue * 1  131/345 (37.97%)  46/172 (26.74%) 
Injection site pain * 1  19/345 (5.51%)  16/172 (9.30%) 
Oedema peripheral * 1  25/345 (7.25%)  8/172 (4.65%) 
Pain * 1  15/345 (4.35%)  12/172 (6.98%) 
Pyrexia * 1  27/345 (7.83%)  6/172 (3.49%) 
Infections and infestations     
Nasopharyngitis * 1  25/345 (7.25%)  9/172 (5.23%) 
Upper respiratory tract infection * 1  20/345 (5.80%)  7/172 (4.07%) 
Investigations     
Aspartate aminotransferase increased * 1  19/345 (5.51%)  8/172 (4.65%) 
Neutrophil count decreased * 1  73/345 (21.16%)  3/172 (1.74%) 
Platelet count decreased * 1  27/345 (7.83%)  0/172 (0.00%) 
White blood cell count decreased * 1  92/345 (26.67%)  5/172 (2.91%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  44/345 (12.75%)  13/172 (7.56%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  45/345 (13.04%)  28/172 (16.28%) 
Back pain * 1  38/345 (11.01%)  25/172 (14.53%) 
Muscle spasms * 1  21/345 (6.09%)  11/172 (6.40%) 
Musculoskeletal chest pain * 1  9/345 (2.61%)  9/172 (5.23%) 
Musculoskeletal pain * 1  20/345 (5.80%)  11/172 (6.40%) 
Myalgia * 1  23/345 (6.67%)  12/172 (6.98%) 
Pain in extremity * 1  33/345 (9.57%)  19/172 (11.05%) 
Nervous system disorders     
Dizziness * 1  37/345 (10.72%)  16/172 (9.30%) 
Dysgeusia * 1  22/345 (6.38%)  3/172 (1.74%) 
Headache * 1  73/345 (21.16%)  30/172 (17.44%) 
Psychiatric disorders     
Anxiety * 1  14/345 (4.06%)  9/172 (5.23%) 
Depression * 1  16/345 (4.64%)  10/172 (5.81%) 
Insomnia * 1  27/345 (7.83%)  12/172 (6.98%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  45/345 (13.04%)  18/172 (10.47%) 
Dyspnoea * 1  37/345 (10.72%)  10/172 (5.81%) 
Epistaxis * 1  19/345 (5.51%)  2/172 (1.16%) 
Oropharyngeal pain * 1  32/345 (9.28%)  9/172 (5.23%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  51/345 (14.78%)  10/172 (5.81%) 
Pruritus * 1  19/345 (5.51%)  10/172 (5.81%) 
Rash * 1  31/345 (8.99%)  7/172 (4.07%) 
Vascular disorders     
Hot flush * 1  51/345 (14.78%)  28/172 (16.28%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01942135     History of Changes
Other Study ID Numbers: A5481023
2013-002580-26 ( EudraCT Number )
First Submitted: September 10, 2013
First Posted: September 13, 2013
Results First Submitted: December 3, 2015
Results First Posted: May 23, 2016
Last Update Posted: November 27, 2019