Trial Outcomes & Findings for A Study Of Palbociclib (PD-0332991) + Letrozole VS. Placebo+ Letrozole For 1st Line Treatment Of Asian Postmenopausal Women With ER+/HER2- Advanced Breast Cancer [PALOMA-4] (NCT NCT02297438)
NCT ID: NCT02297438
Last Updated: 2025-10-27
Results Overview
PFS was based on Kaplan-Meier estimates. PFS was defined as 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 the absence of documented PD, whichever occurred first. PD is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. In this outcome measure, PFS was based on investigator's assessment.
COMPLETED
PHASE3
340 participants
Randomization up to 65 months
2025-10-27
Participant Flow
This was a multicenter, randomized (1:1), double blind, placebo controlled, parallel group Phase 3 trial comparing the efficacy and safety of palbociclib in combination with letrozole versus placebo plus letrozole in Asian postmenopausal women with estrogen receptor positive/human epidermal growth factor receptor 2 negative advanced breast cancer.
Participant milestones
| Measure |
Palbociclib + Letrozole
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Overall Study
STARTED
|
169
|
171
|
|
Overall Study
Received Treatment
|
168
|
171
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
169
|
171
|
Reasons for withdrawal
| Measure |
Palbociclib + Letrozole
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Overall Study
Death
|
79
|
86
|
|
Overall Study
Lost to Follow-up
|
9
|
7
|
|
Overall Study
Withdrawal by Subject
|
7
|
0
|
|
Overall Study
Other
|
9
|
5
|
|
Overall Study
Ongoing
|
65
|
73
|
Baseline Characteristics
A Study Of Palbociclib (PD-0332991) + Letrozole VS. Placebo+ Letrozole For 1st Line Treatment Of Asian Postmenopausal Women With ER+/HER2- Advanced Breast Cancer [PALOMA-4]
Baseline characteristics by cohort
| Measure |
Palbociclib + Letrozole
n=169 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
Total
n=340 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.8 years
STANDARD_DEVIATION 8.5 • n=5 Participants
|
53.7 years
STANDARD_DEVIATION 9.1 • n=7 Participants
|
53.8 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
169 Participants
n=5 Participants
|
171 Participants
n=7 Participants
|
340 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
169 Participants
n=5 Participants
|
171 Participants
n=7 Participants
|
340 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population, including all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
PFS was based on Kaplan-Meier estimates. PFS was defined as 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 the absence of documented PD, whichever occurred first. PD is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. In this outcome measure, PFS was based on investigator's assessment.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=169 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Progression-Free Survival (PFS) Based on Investigator's Assessment
|
21.5 Months
Interval 16.6 to 24.9
|
13.9 Months
Interval 13.7 to 16.6
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population, including all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
PFS was based on Kaplan-Meier estimates. PFS was defined as time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause in the absence of documented progressive disease, whichever occurs first. In this outcome measure, PFS was based on BICR.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=169 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR)
|
21.6 Months
Interval 16.6 to 30.4
|
16.4 Months
Interval 13.8 to 22.2
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population, including all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
OR was defined as a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from randomization until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, OR was based on investigator assessment.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=169 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Percentage of Participants Wiht Objective Response (OR) Based on Investigator Assessment
|
37.3 Percentage of participants
Interval 30.0 to 45.0
|
31.6 Percentage of participants
Interval 24.7 to 39.1
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population with measureable disease at baseline, including the participants, who were randomized, with measureable disease at baseline, and study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
OR was defined as a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from randomization until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, OR was based on investigator assessment.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=145 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=142 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Percentage of Participants With Objective Response (OR) Based on Investigator Assessment (Participants With Measureable Disease at Baseline)
|
43.4 Percentage of participants
Interval 35.2 to 51.9
|
38.0 Percentage of participants
Interval 30.0 to 46.5
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population, including all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
OR was defined as a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from randomization until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, OR was based on BICR.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=169 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Percentage of Participants With Objective Response (OR) Based on Blinded Independent Central Review (BICR)
|
40.2 Percentage of participants
Interval 32.8 to 48.0
|
33.9 Percentage of participants
Interval 26.9 to 41.5
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population with measureable disease at baseline, including the participants, who were randomized, with measureable disease at baseline, and study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
OR was defined as a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from randomization until disease progression or death due to any cause. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, OR was based on BICR.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=128 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=131 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Percentage of Participants With Objective Response (OR) Based on Blinded Independent Central Review (BICR) (Participants With Measureable Disease at Baseline)
|
52.3 Percentage of participants
Interval 43.3 to 61.2
|
43.5 Percentage of participants
Interval 34.9 to 52.4
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population with objective disease response, including all participants who were randomized, with objective disease response and study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
DOR was defined as the time from the first documentation of objective tumor response (complete response \[CR\] or partial response \[PR\]) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. DOR data was censored on the date of the last tumor assessment on study for participants who did not have objective tumor progression and who did not die due to any cause while on study. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, DOR was based on investigator assessment.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=63 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=54 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Duration of Response (DOR) Based on Investigator Assessment (Participants With Objective Disease Response)
|
22.4 Months
Interval 19.4 to 56.2
|
19.4 Months
Interval 13.8 to 24.4
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population with objective disease response, including all participants who were randomized, with objective disease response and study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
DOR was defined as the time from the first documentation of objective tumor response (complete response \[CR\] or partial response \[PR\]) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. DOR data was censored on the date of the last tumor assessment on study for participants who did not have objective tumor progression and who did not die due to any cause while on study. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. In this outcome measure, DOR was based on BICR.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=68 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=58 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Duration of Response (DOR) Based on Blinded Independent Central Review (BICR) (Participants With Objective Disease Response)
|
30.3 Months
Interval 19.4 to
As 50% participants in this analysis set was censored, the upper bound of 95% confidence interval was not reached.
|
24.9 Months
Interval 11.5 to 36.1
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population, including all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
DC/CBR was defined as CR, PR, or stable disease (SD) \>=24 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) recorded in the time period between randomization and disease progression or death to any cause. CR was defined as complete disappearance of all target lesions except for nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). No new lesions. The PR was defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. SD was defined as not qualifying for CR, PR, PD. PD is defined using RECIST v1.1 as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. In this outcome measure, DC/CBR was based on investigator assessment.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=169 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Investigator Assessment
|
79.3 Percentage of participants
Interval 72.4 to 85.1
|
80.1 Percentage of participants
Interval 73.3 to 85.8
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population with measureable disease at baseline, including the participants, who were randomized, with measureable disease at baseline, and study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
DC/CBR was defined as CR, PR, or stable disease (SD) \>=24 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) recorded in the time period between randomization and disease progression or death to any cause. CR was defined as complete disappearance of all target lesions except for nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. SD was defined as not qualifying for CR, PR, PD. PD is defined using RECIST v1.1 as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. In this outcome measure, DC/CBR was based on investigator assessment.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=145 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=142 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Investigator Assessment (Participants With Measureable Disease at Baseline)
|
77.9 Percentage of participants
Interval 70.3 to 84.4
|
79.6 Percentage of participants
Interval 72.0 to 85.9
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population, including all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
DC/CBR was defined as CR, PR, or stable disease (SD) \>=24 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) recorded in the time period between randomization and disease progression or death to any cause. CR was defined as complete disappearance of all target lesions except for nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. SD was defined as not qualifying for CR, PR, PD. PD is defined using RECIST v1.1 as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. In this outcome measure, DC/CBR was based on BICR.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=169 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Blinded Independent Central Review (BICR)
|
76.9 Percentage of participants
Interval 69.8 to 83.0
|
73.1 Percentage of participants
Interval 65.8 to 79.6
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population with measureable disease at baseline, including the participants, who were randomized, with measureable disease at baseline, and study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
DC/CBR was defined as CR, PR, or stable disease (SD) \>=24 weeks according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) recorded in the time period between randomization and disease progression or death to any cause. CR was defined as complete disappearance of all target lesions except for nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). No new lesions. The PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No new lesions. SD was defined as not qualifying for CR, PR, PD. PD is defined using RECIST v1.1 as a 20% increase in the sum of of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. In this outcome measure, DC/CBR was based on BICR.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=128 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=131 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Percentage of Participants With Disease Control/Clinical Benefit Response (DC/CBR) Based on Blinded Independent Central Review (BICR) (Participants With Measureable Disease at Baseline)
|
78.1 Percentage of participants
Interval 70.0 to 84.9
|
71.8 Percentage of participants
Interval 63.2 to 79.3
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population, including all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
OS was 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. OS was assessed using Kaplan-Meier methods.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=169 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Overall Survival (OS)
|
51.7 Months
Interval 43.0 to
As 50% participants in this analysis set was censored, the upper bound of 95% confidence interval was not reached.
|
51.5 Months
Interval 41.0 to
As 50% participants in this analysis set was censored, the upper bound of 95% confidence interval was not reached.
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was intent-to-treat (ITT) population, including all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
OS was 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. The 1-year survival probability was estimated using the Kaplan-Meier method and a 2-sided 95% confidence interval (CI) for the log \[-log(1 year survival probability)\] was be calculated using a normal approximation, and then back transformed to give a CI for the 1-year survival probability itself. The 2-year, and 3-year survival probabilities were estimated similarly.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=169 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
1-Year, 2-Year and 3-Year Survival Probability
1-year survival probability
|
92.8 Percentage of participants
Interval 87.6 to 95.8
|
90.5 Percentage of participants
Interval 85.0 to 94.1
|
|
1-Year, 2-Year and 3-Year Survival Probability
2-year survival probability
|
80.3 Percentage of participants
Interval 73.3 to 85.6
|
78.0 Percentage of participants
Interval 71.0 to 83.6
|
|
1-Year, 2-Year and 3-Year Survival Probability
3-year survival probability
|
67.1 Percentage of participants
Interval 59.1 to 73.8
|
60.6 Percentage of participants
Interval 52.7 to 67.5
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was as-treated (AT) population, including all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Participants were counted only once per treatment in each row.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=168 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants with AEs
|
168 Participants
|
155 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants with SAEs
|
26 Participants
|
16 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants with Grade 3 or 4 AEs
|
152 Participants
|
38 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants with Grade 5 AEs
|
4 Participants
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants discontinued study due to AEs
|
13 Participants
|
5 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants discontinued Palbociclib/Placebo or Letrozole due to AEs
|
11 Participants
|
4 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants discontinued Palbociclib/Placebo due to AEs
|
11 Participants
|
4 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants discontinued Letrozole due to AEs
|
10 Participants
|
3 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants temporarily discontinued Palbociclib/Placebo due to AEs
|
136 Participants
|
17 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants temporarily discontinued Letrozole due to AEs
|
11 Participants
|
9 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants with dose reduction of Palbociclib/Placebo due to AEs
|
16 Participants
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants with dose reduction and temporary discontinuations of Palbociclib/Placebo due to AEs
|
38 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was as-treated (AT) population, including all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to treatment was assessed by the investigator (Yes/No). Participants were counted only once per treatment in each row.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=168 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Participants with AEs
|
167 Participants
|
123 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Participants with SAEs
|
8 Participants
|
3 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Participants with Grade 3 or 4 AEs
|
149 Participants
|
18 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Participants with Grade 5 AEs
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Participants discontinued study due to AEs
|
6 Participants
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Participants discontinued Palbociclib/Placebo or Letrozole due to AEs
|
5 Participants
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Participants discontinued due to AEs related to Palbociclib/Placebo
|
5 Participants
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Participants discontinued due to AEs related to Letrozole
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Participants temporarily discontinued Palbociclib/Placebo due to AEs
|
132 Participants
|
11 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Participants temporarily discontinued Letrozole due to AEs
|
7 Participants
|
5 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Participants with dose reduction of Palbociclib/Placebo due to AEs
|
15 Participants
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
Participants with dose reduction and temporary discontinuations of Palbociclib/Placebo due to AEs
|
37 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was as-treated (AT) population, including all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.
The laboratory results were graded according to the National Cancer Institute (NCI) CTCAE v4.0 severity grade. Shift tables were provided to examine the distribution of laboratory toxicities. The following hematology parameters had met the criteria of CTCAE grade shift change from Grade \<=2 at baseline to Grade 3 or 4 post baseline: neutrophils (absolute), white blood cells, platelets, anemia and hemoglobin increased.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=168 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Hematology
Neutrophils (absolute)
|
143 Participants
|
2 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Hematology
White blood cells
|
77 Participants
|
1 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Hematology
Platelets
|
13 Participants
|
1 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Hematology
Anemia
|
10 Participants
|
3 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Hematology
Hemoglobin increased
|
3 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Randomization up to 65 monthsPopulation: This was as-treated (AT) population, including all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.
The laboratory results were graded according to the National Cancer Institute (NCI) CTCAE v4.0 severity grade. Shift tables were provided to examine the distribution of laboratory toxicities. The following chemistry parameters had met the criteria of CTCAE grade shift change from Grade \<=2 at baseline to Grade 3 or 4 post baseline: alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), bilirubin (total), creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, and hyponatremia.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=168 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Hypoalbuminemia
|
0 Participants
|
0 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Hypocalcemia
|
1 Participants
|
1 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Hypoglycemia
|
0 Participants
|
1 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Hypokalemia
|
3 Participants
|
6 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Hypomagnesemia
|
3 Participants
|
1 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Hyponatremia
|
11 Participants
|
2 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
ALT
|
9 Participants
|
1 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Alkaline phosphatase
|
0 Participants
|
2 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
AST
|
9 Participants
|
6 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Bilirubin (total)
|
2 Participants
|
2 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Creatinine
|
1 Participants
|
0 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Hypercalcemia
|
1 Participants
|
2 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Hyperglycemia
|
1 Participants
|
1 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Hyperkalemia
|
1 Participants
|
0 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Hypermagnesemia
|
10 Participants
|
8 Participants
|
|
Number of Participants With Postbaseline Laboratory Abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) Grade 3 or 4 (Participants With Baseline Laboratory Abnormalities of CTCAE Grade <=2) - Chemistry
Hypernatremia
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Pre-dose on Day 14 of Cycle 1 and Cycle 2Population: This was a subset of as-treated (AT) population (participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received), including all participants who are treated with palbociclib and have at least 1 measured plasma concentration.
Summary of palbociclib trough concentrations
Outcome measures
| Measure |
Palbociclib + Letrozole
n=143 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Trough Plasma Concentration of Palbociclib
Cycle 1
|
81.1 ng/mL
Geometric Coefficient of Variation 29
|
—
|
|
Trough Plasma Concentration of Palbociclib
Cycle 2
|
77.4 ng/mL
Geometric Coefficient of Variation 43
|
—
|
|
Trough Plasma Concentration of Palbociclib
Average trough concentration
|
80.2 ng/mL
Geometric Coefficient of Variation 36
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Cycle 65 Day 1Population: This was a subset of intent-to-treat (ITT) population (participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized), who had both baseline and who completed all 5 items needed to calculated the index-based summary score ata the respective cycle.
The EQ-5D is a 6-item instrument designed to assess health status in terms of a single index value or utility score. It consists of 5 descriptors of current health state (mobility, self care, usual activities, pain/discomfort, and anxiety/depression); a participant was asked to rate each state on a 3 level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/impairment.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=166 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 3 Day 1
|
0.012 Units on a scale
Interval -0.01 to 0.03
|
0.011 Units on a scale
Interval -0.01 to 0.03
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 57 Day 1
|
-0.043 Units on a scale
Interval -0.13 to 0.04
|
-0.141 Units on a scale
Interval -0.23 to -0.05
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 63 Day 1
|
-0.049 Units on a scale
Interval -0.14 to 0.04
|
-0.158 Units on a scale
Interval -0.26 to -0.06
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 2 Day 1
|
0.013 Units on a scale
Interval -0.01 to 0.03
|
0.014 Units on a scale
Interval -0.01 to 0.03
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 5 Day 1
|
0.010 Units on a scale
Interval -0.01 to 0.03
|
0.005 Units on a scale
Interval -0.01 to 0.03
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 7 Day 1
|
0.008 Units on a scale
Interval -0.01 to 0.03
|
0.000 Units on a scale
Interval -0.02 to 0.02
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 9 Day 1
|
0.006 Units on a scale
Interval -0.02 to 0.03
|
-0.006 Units on a scale
Interval -0.03 to 0.02
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 11 Day 1
|
0.004 Units on a scale
Interval -0.02 to 0.03
|
-0.012 Units on a scale
Interval -0.04 to 0.01
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 13 Day 1
|
0.02 Units on a scale
Interval -0.02 to 0.03
|
-0.017 Units on a scale
Interval -0.04 to 0.01
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 15 Day 1
|
0.000 Units on a scale
Interval -0.03 to 0.03
|
-0.023 Units on a scale
Interval -0.05 to 0.01
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 17 Day 1
|
-0.002 Units on a scale
Interval -0.03 to 0.03
|
-0.029 Units on a scale
Interval -0.06 to 0.0
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 19 Day 1
|
-0.004 Units on a scale
Interval -0.04 to 0.03
|
-0.034 Units on a scale
Interval -0.07 to 0.0
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 21 Day 1
|
-0.006 Units on a scale
Interval -0.04 to 0.03
|
-0.040 Units on a scale
Interval -0.08 to 0.0
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 23 Day 1
|
-0.008 Units on a scale
Interval -0.05 to 0.03
|
-0.045 Units on a scale
Interval -0.08 to -0.01
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 25 Day 1
|
-0.010 Units on a scale
Interval -0.05 to 0.03
|
-0.051 Units on a scale
Interval -0.09 to -0.01
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 27 Day 1
|
-0.012 Units on a scale
Interval -0.05 to 0.03
|
-0.057 Units on a scale
Interval -0.1 to -0.01
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 29 Day 1
|
-0.014 Units on a scale
Interval -0.06 to 0.03
|
-0.062 Units on a scale
Interval -0.11 to -0.02
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 31 Day 1
|
-0.016 Units on a scale
Interval -0.06 to 0.03
|
-0.068 Units on a scale
Interval -0.12 to -0.02
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 33 Day 1
|
-0.018 Units on a scale
Interval -0.07 to 0.03
|
-0.074 Units on a scale
Interval -0.13 to -0.02
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 35 Day 1
|
-0.020 Units on a scale
Interval -0.07 to 0.03
|
-0.079 Units on a scale
Interval -0.13 to -0.02
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 37 Day 1
|
-0.022 Units on a scale
Interval -0.08 to 0.03
|
-0.085 Units on a scale
Interval -0.14 to -0.03
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 39 Day 1
|
-0.024 Units on a scale
Interval -0.08 to 0.03
|
-0.090 Units on a scale
Interval -0.15 to -0.03
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 41 Day 1
|
-0.027 Units on a scale
Interval -0.09 to 0.03
|
-0.096 Units on a scale
Interval -0.16 to -0.03
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 43 Day 1
|
-0.029 Units on a scale
Interval -0.09 to 0.04
|
-0.102 Units on a scale
Interval -0.17 to -0.03
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 45 Day 1
|
-0.031 Units on a scale
Interval -0.1 to 0.04
|
-0.107 Units on a scale
Interval -0.18 to -0.04
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 47 Day 1
|
-0.033 Units on a scale
Interval -0.1 to 0.04
|
-0.113 Units on a scale
Interval -0.19 to -0.04
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 49 Day 1
|
-0.035 Units on a scale
Interval -0.11 to 0.04
|
-0.119 Units on a scale
Interval -0.2 to -0.04
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 51 Day 1
|
-0.037 Units on a scale
Interval -0.11 to 0.04
|
-0.124 Units on a scale
Interval -0.2 to -0.04
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 53 Day 1
|
-0.039 Units on a scale
Interval -0.12 to 0.04
|
-0.130 Units on a scale
Interval -0.21 to -0.05
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 55 Day 1
|
-0.041 Units on a scale
Interval -0.12 to 0.04
|
-0.136 Units on a scale
Interval -0.22 to -0.05
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 59 Day 1
|
-0.045 Units on a scale
Interval -0.13 to 0.04
|
-0.147 Units on a scale
Interval -0.24 to -0.05
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 61 Day 1
|
-0.047 Units on a scale
Interval -0.14 to 0.04
|
-0.152 Units on a scale
Interval -0.25 to -0.06
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life 5-Dimension Scale (EQ-5D) Index Scores
Cycle 65 Day 1
|
-0.051 Units on a scale
Interval -0.15 to 0.04
|
-0.164 Units on a scale
Interval -0.27 to -0.06
|
SECONDARY outcome
Timeframe: Baseline up to Cycle 65 Day 1Population: This was a subset of intent-to-treat (ITT) population (participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized), who had both baseline and who completed all 5 items needed to calculated the index-based summary score ata the respective cycle.
The EQ VAS recorded the participant's self rated questionnaire to assess generic health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state). Published weights were available that allow for the creation of a single summary score.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=166 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 9 Day 1
|
3.589 Units on a scale
Interval 2.09 to 5.09
|
1.543 Units on a scale
Interval 0.05 to 3.03
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 15 Day 1
|
4.052 Units on a scale
Interval 2.46 to 5.65
|
1.271 Units on a scale
Interval -0.34 to 2.88
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 43 Day 1
|
6.217 Units on a scale
Interval 3.36 to 9.07
|
0.000 Units on a scale
Interval -3.06 to 3.06
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 45 Day 1
|
6.372 Units on a scale
Interval 3.4 to 9.34
|
-0.091 Units on a scale
Interval -3.28 to 3.1
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 63 Day 1
|
7.763 Units on a scale
Interval 3.71 to 11.82
|
-0.907 Units on a scale
Interval -5.31 to 3.5
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 2 Day 1
|
3.047 Units on a scale
Interval 1.53 to 4.57
|
1.861 Units on a scale
Interval 0.35 to 3.37
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 3 Day 1
|
3.125 Units on a scale
Interval 1.62 to 4.63
|
1.815 Units on a scale
Interval 0.32 to 3.31
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 5 Day 1
|
3.279 Units on a scale
Interval 1.79 to 4.77
|
1.724 Units on a scale
Interval 0.24 to 3.21
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 7 Day 1
|
3.434 Units on a scale
Interval 1.94 to 4.92
|
1.634 Units on a scale
Interval 0.16 to 3.11
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 11 Day 1
|
3.743 Units on a scale
Interval 2.22 to 5.26
|
1.452 Units on a scale
Interval -0.06 to 2.97
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 13 Day 1
|
3.898 Units on a scale
Interval 2.35 to 5.45
|
1.361 Units on a scale
Interval -0.19 to 2.92
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 17 Day 1
|
4.207 Units on a scale
Interval 2.56 to 5.85
|
1.180 Units on a scale
Interval -0.49 to 2.85
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 19 Day 1
|
4.362 Units on a scale
Interval 2.65 to 6.07
|
1.089 Units on a scale
Interval -0.65 to 2.83
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 21 Day 1
|
4.516 Units on a scale
Interval 2.74 to 6.29
|
0.998 Units on a scale
Interval -0.83 to 2.82
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 23 Day 1
|
4.671 Units on a scale
Interval 2.82 to 6.52
|
0.908 Units on a scale
Interval -1.01 to 2.82
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 25 Day 1
|
4.826 Units on a scale
Interval 2.89 to 6.76
|
0.817 Units on a scale
Interval -1.2 to 2.83
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 27 Day 1
|
4.980 Units on a scale
Interval 2.96 to 7.0
|
0.726 Units on a scale
Interval -1.39 to 2.84
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 29 Day 1
|
5.135 Units on a scale
Interval 3.02 to 7.25
|
0.635 Units on a scale
Interval -1.59 to 2.86
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 31 Day 1
|
5.289 Units on a scale
Interval 3.08 to 7.5
|
0.545 Units on a scale
Interval -1.79 to 2.88
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 33 Day 1
|
5.444 Units on a scale
Interval 3.13 to 7.76
|
0.454 Units on a scale
Interval -1.99 to 2.9
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 35 Day 1
|
5.599 Units on a scale
Interval 3.18 to 8.02
|
0.363 Units on a scale
Interval -2.2 to 2.93
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 37 Day 1
|
5.753 Units on a scale
Interval 3.23 to 8.28
|
0.272 Units on a scale
Interval -2.42 to 2.96
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 39 Day 1
|
5.908 Units on a scale
Interval 3.28 to 8.54
|
0.182 Units on a scale
Interval -2.63 to 2.99
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 41 Day 1
|
6.063 Units on a scale
Interval 3.32 to 8.81
|
0.091 Units on a scale
Interval -2.85 to 3.03
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 47 Day 1
|
6.526 Units on a scale
Interval 3.44 to 9.61
|
-0.181 Units on a scale
Interval -3.51 to 3.14
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 49 Day 1
|
6.681 Units on a scale
Interval 3.48 to 9.89
|
-0.272 Units on a scale
Interval -3.73 to 3.18
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 51 Day 1
|
6.836 Units on a scale
Interval 3.51 to 10.16
|
-0.363 Units on a scale
Interval -3.95 to 3.23
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 53 Day 1
|
6.990 Units on a scale
Interval 3.55 to 10.43
|
-0.454 Units on a scale
Interval -4.18 to 3.27
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 55 Day 1
|
7.145 Units on a scale
Interval 3.58 to 10.71
|
-0.544 Units on a scale
Interval -4.4 to 3.31
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 57 Day 1
|
7.300 Units on a scale
Interval 3.61 to 10.99
|
-0.635 Units on a scale
Interval -4.63 to 3.36
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 59 Day 1
|
7.454 Units on a scale
Interval 3.64 to 11.26
|
-0.726 Units on a scale
Interval -4.86 to 3.41
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 61 Day 1
|
7.609 Units on a scale
Interval 3.68 to 11.54
|
-0.817 Units on a scale
Interval -5.08 to 3.45
|
|
Model Estimated Mean Change From Baseline in Euro Quality of Life (EQ) Visual Analog Scale (VAS) Scores
Cycle 65 Day 1
|
7.918 Units on a scale
Interval 3.74 to 12.1
|
-0.998 Units on a scale
Interval -5.54 to 3.55
|
SECONDARY outcome
Timeframe: Baseline up to Cycle 65 Day 1Population: This was a subset of intent-to-treat (ITT) population (participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized), who had both baseline and who completed \>80% of the corresponding questions and had valid scores for the relevant subscales.
The Functional Assessment of Cancer Therapy (FACT) is a modular approach to assess participant health related quality of life using a "core" set of questions (FACT-G) as well as a cancer site specific module. The FACT-G was a 27-item compilation of general questions divided into 4 domains: Physical Well Being, Social/Family Well Being, Emotional Well Being, and Functional Well Being. The FACT-B consists of the FACT-G (27 items) and a breast specific module: a 10-item instrument designed to assess participant concerns relating to breast cancer. For all questions, participants were asked to respond to a 5-level scale ranging from 0=Not at all to 4=Very much. FACT-B total score = FACT-G + Breast Cancer Subscale. As each of the items ranges from 0-4, the range of possible scores is 0-148, with 0 being the worst possible score and 148 the best. A positive change of the total score indicated improvement from baseline and a negative change indicated deterioration.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=166 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 2 Day 1
|
1.618 Units on a scale
Interval -0.15 to 3.39
|
1.021 Units on a scale
Interval -0.74 to 2.78
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 3 Day 1
|
1.441 Units on a scale
Interval -0.32 to 3.2
|
0.850 Units on a scale
Interval -0.9 to 2.6
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 5 Day 1
|
1.087 Units on a scale
Interval -0.69 to 2.86
|
0.510 Units on a scale
Interval -1.25 to 2.27
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 7 Day 1
|
0.732 Units on a scale
Interval -1.07 to 2.53
|
0.169 Units on a scale
Interval -1.62 to 1.96
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 9 Day 1
|
0.378 Units on a scale
Interval -1.48 to 2.23
|
-0.171 Units on a scale
Interval -2.02 to 1.68
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 11 Day 1
|
0.024 Units on a scale
Interval -1.9 to 1.95
|
-0.512 Units on a scale
Interval -2.44 to 1.41
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 13 Day 1
|
-0.331 Units on a scale
Interval -2.34 to 1.68
|
-0.852 Units on a scale
Interval -2.88 to 1.17
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 15 Day 1
|
-0.685 Units on a scale
Interval -2.8 to 1.43
|
-1.193 Units on a scale
Interval -3.33 to 0.95
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 17 Day 1
|
-1.039 Units on a scale
Interval -3.27 to 1.19
|
-1.534 Units on a scale
Interval -3.8 to 0.74
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 19 Day 1
|
-1.393 Units on a scale
Interval -3.75 to 0.96
|
-1.874 Units on a scale
Interval -4.29 to 0.54
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 21 Day 1
|
-1.748 Units on a scale
Interval -4.24 to 0.75
|
-2.215 Units on a scale
Interval -4.78 to 0.35
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 23 Day 1
|
-2.102 Units on a scale
Interval -4.74 to 0.54
|
-2.555 Units on a scale
Interval -5.28 to 0.17
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 25 Day 1
|
-2.456 Units on a scale
Interval -5.24 to 0.33
|
-2.896 Units on a scale
Interval -5.79 to 0.0
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 27 Day 1
|
-2.810 Units on a scale
Interval -5.76 to 0.13
|
-3.326 Units on a scale
Interval -6.31 to -0.16
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 29 Day 1
|
-3.165 Units on a scale
Interval -6.27 to -0.06
|
-3.577 Units on a scale
Interval -6.83 to -0.33
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 31 Day 1
|
-3.519 Units on a scale
Interval -6.79 to -0.25
|
-3.918 Units on a scale
Interval -7.35 to -0.48
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 33 Day 1
|
-3.873 Units on a scale
Interval -7.31 to -0.43
|
-4.258 Units on a scale
Interval -7.88 to -0.64
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 35 Day 1
|
-4.227 Units on a scale
Interval -7.84 to -0.62
|
-4.599 Units on a scale
Interval -8.41 to -0.79
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 37 Day 1
|
-4.582 Units on a scale
Interval -8.37 to -0.8
|
-4.939 Units on a scale
Interval -8.95 to -0.93
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 39 Day 1
|
-4.936 Units on a scale
Interval -8.9 to -0.97
|
-5.280 Units on a scale
Interval -9.48 to -1.08
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 41 Day 1
|
-5.290 Units on a scale
Interval -9.43 to -1.15
|
-5.620 Units on a scale
Interval -10.02 to -1.22
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 43 Day 1
|
-5.644 Units on a scale
Interval -9.97 to -1.32
|
-5.961 Units on a scale
Interval -10.56 to -1.36
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 45 Day 1
|
-5.999 Units on a scale
Interval -10.5 to -1.5
|
-6.301 Units on a scale
Interval -11.1 to -1.5
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 47 Day 1
|
-6.353 Units on a scale
Interval -11.04 to -1.67
|
-6.642 Units on a scale
Interval -11.64 to -1.64
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 49 Day 1
|
-6.707 Units on a scale
Interval -11.58 to -1.84
|
-6.983 Units on a scale
Interval -12.18 to -1.78
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 51 Day 1
|
-7.061 Units on a scale
Interval -12.12 to -2.0
|
-7.323 Units on a scale
Interval -12.73 to -1.92
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 53 Day 1
|
-7.416 Units on a scale
Interval -12.66 to -2.17
|
-7.664 Units on a scale
Interval -13.27 to -2.05
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 55 Day 1
|
-7.770 Units on a scale
Interval -13.2 to -2.34
|
-8.004 Units on a scale
Interval -13.82 to -2.19
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 57 Day 1
|
-8.124 Units on a scale
Interval -13.74 to -2.51
|
-8.345 Units on a scale
Interval -14.37 to -2.32
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 59 Day 1
|
-8.478 Units on a scale
Interval -14.29 to -2.67
|
-8.685 Units on a scale
Interval -14.91 to -2.46
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 61 Day 1
|
-8.833 Units on a scale
Interval -14.83 to -2.84
|
-9.026 Units on a scale
Interval -15.46 to -2.59
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 63 Day 1
|
-9.187 Units on a scale
Interval -15.37 to -3.0
|
-9.367 Units on a scale
Interval -16.01 to -2.72
|
|
Model Estimated Mean Changes From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Total Score
Cycle 65 Day 1
|
-9.541 Units on a scale
Interval -15.92 to -3.16
|
-9.707 Units on a scale
Interval -16.56 to -2.86
|
SECONDARY outcome
Timeframe: BaselinePopulation: This was a subset of as-treated (AT) population (participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received), who had both baseline and at least 1 follow-up values for Ki67.
Archived formalin-fixed paraffin embedded (FFPE) specimen from the original diagnostic tumor tissue was collected and sent to the sponsor-designated central laboratories for assessment of Ki67 associated with sensitivity and/or resistance to Palbociclib.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=146 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=156 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Median Baseline Percent (%) Positive Cells for Ki67
|
30.0 Percentage of Ki67 positive cells
Interval 0.0 to 95.0
|
27.5 Percentage of Ki67 positive cells
Interval 0.0 to 95.0
|
SECONDARY outcome
Timeframe: BaselinePopulation: This was a subset of as-treated (AT) population (participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received), who had both baseline and at least 1 follow-up values for ER.
Archived formalin-fixed paraffin embedded (FFPE) specimen from the original diagnostic tumor tissue was collected and sent to the sponsor-designated central laboratories for assessment of ER associated with sensitivity and/or resistance to Palbociclib.
Outcome measures
| Measure |
Palbociclib + Letrozole
n=168 Participants
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 Participants
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Number of Participants With Detection in Estrogen Receptor (ER)
Positive
|
152 Participants
|
162 Participants
|
|
Number of Participants With Detection in Estrogen Receptor (ER)
Negative
|
2 Participants
|
1 Participants
|
|
Number of Participants With Detection in Estrogen Receptor (ER)
Unknown
|
14 Participants
|
8 Participants
|
Adverse Events
Palbociclib + Letrozole
Placebo + Letrozole
Serious adverse events
| Measure |
Palbociclib + Letrozole
n=168 participants at risk
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 participants at risk
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Ear and labyrinth disorders
Ear disorder
|
0.00%
0/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Endocrine disorders
Thyroid mass
|
0.00%
0/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
General disorders
Clinical death
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
General disorders
Disease progression
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
General disorders
Pyrexia
|
1.2%
2/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Hepatobiliary disorders
Drug-induced liver injury
|
0.00%
0/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Hepatobiliary disorders
Liver injury
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Infections and infestations
Endocarditis
|
0.00%
0/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Infections and infestations
Erysipelas
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Infections and infestations
Pneumonia
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
1.2%
2/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Infections and infestations
Pyelonephritis acute
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Infections and infestations
Urinary tract infection
|
1.2%
2/168 • 65 months
Participants were only counted once per treatment for each category
|
1.2%
2/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
1.2%
2/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Injury, poisoning and procedural complications
Fall
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Injury, poisoning and procedural complications
Fracture
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Platelet count decreased
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/168 • 65 months
Participants were only counted once per treatment for each category
|
1.2%
2/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression
|
1.2%
2/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer stage II
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Nervous system disorders
Dizziness
|
0.00%
0/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.58%
1/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Respiratory, thoracic and mediastinal disorders
Hydrothorax
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.8%
3/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Vascular disorders
Hypertension
|
0.60%
1/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
Other adverse events
| Measure |
Palbociclib + Letrozole
n=168 participants at risk
Participants were planned to receive palbociclib 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for palbociclib and for letrozole were 1872 days and 1872 days, respectively.
|
Placebo + Letrozole
n=171 participants at risk
Participants were planned to receive placebo 125 mg orally once a day (QD) for 21 days of every 28-day cycle followed by 7 days off treatment together with letrozole 2.5 mg orally QD continuously. The maximum duration of treatment for placebo and for letrozole were 1834 days and 1834 days, respectively.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
38.7%
65/168 • 65 months
Participants were only counted once per treatment for each category
|
7.6%
13/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Blood and lymphatic system disorders
Leukopenia
|
28.6%
48/168 • 65 months
Participants were only counted once per treatment for each category
|
4.7%
8/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Blood and lymphatic system disorders
Neutropenia
|
44.0%
74/168 • 65 months
Participants were only counted once per treatment for each category
|
7.0%
12/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
13.7%
23/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Eye disorders
Cataract
|
7.1%
12/168 • 65 months
Participants were only counted once per treatment for each category
|
5.8%
10/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Eye disorders
Lenticular opacities
|
5.4%
9/168 • 65 months
Participants were only counted once per treatment for each category
|
4.1%
7/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Gastrointestinal disorders
Constipation
|
3.6%
6/168 • 65 months
Participants were only counted once per treatment for each category
|
5.8%
10/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Gastrointestinal disorders
Diarrhoea
|
10.7%
18/168 • 65 months
Participants were only counted once per treatment for each category
|
8.2%
14/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Gastrointestinal disorders
Mouth ulceration
|
7.7%
13/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Gastrointestinal disorders
Nausea
|
9.5%
16/168 • 65 months
Participants were only counted once per treatment for each category
|
8.8%
15/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Gastrointestinal disorders
Toothache
|
6.0%
10/168 • 65 months
Participants were only counted once per treatment for each category
|
1.8%
3/171 • 65 months
Participants were only counted once per treatment for each category
|
|
General disorders
Fatigue
|
10.1%
17/168 • 65 months
Participants were only counted once per treatment for each category
|
8.2%
14/171 • 65 months
Participants were only counted once per treatment for each category
|
|
General disorders
Influenza like illness
|
7.7%
13/168 • 65 months
Participants were only counted once per treatment for each category
|
4.7%
8/171 • 65 months
Participants were only counted once per treatment for each category
|
|
General disorders
Oedema peripheral
|
5.4%
9/168 • 65 months
Participants were only counted once per treatment for each category
|
3.5%
6/171 • 65 months
Participants were only counted once per treatment for each category
|
|
General disorders
Pain
|
6.0%
10/168 • 65 months
Participants were only counted once per treatment for each category
|
7.6%
13/171 • 65 months
Participants were only counted once per treatment for each category
|
|
General disorders
Pyrexia
|
14.3%
24/168 • 65 months
Participants were only counted once per treatment for each category
|
5.8%
10/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Infections and infestations
Nasopharyngitis
|
7.7%
13/168 • 65 months
Participants were only counted once per treatment for each category
|
5.8%
10/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Infections and infestations
Upper respiratory tract infection
|
11.3%
19/168 • 65 months
Participants were only counted once per treatment for each category
|
11.7%
20/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
56/168 • 65 months
Participants were only counted once per treatment for each category
|
32.7%
56/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Aspartate aminotransferase increased
|
34.5%
58/168 • 65 months
Participants were only counted once per treatment for each category
|
28.1%
48/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Bilirubin conjugated increased
|
6.5%
11/168 • 65 months
Participants were only counted once per treatment for each category
|
4.1%
7/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Blood alkaline phosphatase increased
|
5.4%
9/168 • 65 months
Participants were only counted once per treatment for each category
|
8.2%
14/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Blood bilirubin increased
|
6.5%
11/168 • 65 months
Participants were only counted once per treatment for each category
|
7.6%
13/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Blood creatinine increased
|
6.0%
10/168 • 65 months
Participants were only counted once per treatment for each category
|
1.2%
2/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Blood lactate dehydrogenase increased
|
6.5%
11/168 • 65 months
Participants were only counted once per treatment for each category
|
4.7%
8/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Electrocardiogram QT prolonged
|
14.9%
25/168 • 65 months
Participants were only counted once per treatment for each category
|
8.2%
14/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Gamma-glutamyltransferase increased
|
10.1%
17/168 • 65 months
Participants were only counted once per treatment for each category
|
7.0%
12/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Haemoglobin decreased
|
11.3%
19/168 • 65 months
Participants were only counted once per treatment for each category
|
1.8%
3/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Low density lipoprotein increased
|
4.8%
8/168 • 65 months
Participants were only counted once per treatment for each category
|
5.3%
9/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Neutrophil count decreased
|
65.5%
110/168 • 65 months
Participants were only counted once per treatment for each category
|
11.1%
19/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Platelet count decreased
|
41.7%
70/168 • 65 months
Participants were only counted once per treatment for each category
|
4.1%
7/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Red blood cell count decreased
|
6.0%
10/168 • 65 months
Participants were only counted once per treatment for each category
|
1.2%
2/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
Weight increased
|
10.7%
18/168 • 65 months
Participants were only counted once per treatment for each category
|
7.0%
12/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Investigations
White blood cell count decreased
|
63.1%
106/168 • 65 months
Participants were only counted once per treatment for each category
|
8.8%
15/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
9.5%
16/168 • 65 months
Participants were only counted once per treatment for each category
|
5.8%
10/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
7.1%
12/168 • 65 months
Participants were only counted once per treatment for each category
|
5.8%
10/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
10.7%
18/168 • 65 months
Participants were only counted once per treatment for each category
|
6.4%
11/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.3%
19/168 • 65 months
Participants were only counted once per treatment for each category
|
15.2%
26/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.5%
16/168 • 65 months
Participants were only counted once per treatment for each category
|
7.0%
12/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
4.2%
7/168 • 65 months
Participants were only counted once per treatment for each category
|
5.8%
10/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.9%
15/168 • 65 months
Participants were only counted once per treatment for each category
|
4.7%
8/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.3%
14/168 • 65 months
Participants were only counted once per treatment for each category
|
7.0%
12/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Nervous system disorders
Dizziness
|
10.1%
17/168 • 65 months
Participants were only counted once per treatment for each category
|
6.4%
11/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Nervous system disorders
Headache
|
7.7%
13/168 • 65 months
Participants were only counted once per treatment for each category
|
4.1%
7/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Psychiatric disorders
Insomnia
|
6.0%
10/168 • 65 months
Participants were only counted once per treatment for each category
|
7.6%
13/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.1%
27/168 • 65 months
Participants were only counted once per treatment for each category
|
12.9%
22/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.0%
10/168 • 65 months
Participants were only counted once per treatment for each category
|
1.2%
2/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.4%
9/168 • 65 months
Participants were only counted once per treatment for each category
|
0.00%
0/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
11.9%
20/168 • 65 months
Participants were only counted once per treatment for each category
|
6.4%
11/171 • 65 months
Participants were only counted once per treatment for each category
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.5%
11/168 • 65 months
Participants were only counted once per treatment for each category
|
5.3%
9/171 • 65 months
Participants were only counted once per treatment for each category
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER