Breast Cancer
Conditions
Keywords
Hormone receptor positive advanced breast cancer
Brief summary
A study of palbociclib in combination with letrozole as treatment of post-menopausal women with hormone receptor-positive, her2-negative advanced breast cancer for whom letrozole therapy is deemed appropriate.
Detailed description
To provide access to palbociclib to post-menopausal patients with hormone receptor-positive \[HR(+)\], HER2-negative \[HER2(-)\] ABC who are deemed appropriate for letrozole therapy.
Interventions
DRUGPalbociclib
125 mg/d capsules orally for 3 out of 4 weeks in repeated cycles
DRUGLetrozole
2.5 mg/d tablets orally on a continuous regimen
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Post-menopausal women (\>=18 years of age) with proven diagnosis of advanced carcinoma of the breast (ER(+) and/or PgR(+) and HER2(-)) who are appropriate for letrozole therapy (in the first-line advanced/metastatic disease setting). * Eastern Cooperative Oncology Group (ECOG) performance status 0-2. * Adequate bone marrow, liver, and renal function.
Exclusion criteria
* Prior treatment with any CDK inhibitor . * QTc \>480 msec; history of QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes. * High cardiovascular risk, including, but not limited to myocardial infarction, severe/unstable angina, severe cardiac dysrhythmias, and symptomatic pulmonary embolism in the past 6 months of enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Baseline up to 28 days after last dose of study treatment, an average of 14 months | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as treatment emergent adverse events (TEAEs). AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity. A serious adverse event (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. |
| Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Baseline up to 28 days after last dose of study treatment, an average of 14 months | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity. |
| Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Baseline up to 28 days after last dose of study treatment, an average of 14 months | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity. An 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. Palbociclib-related TEAEs were determined by the investigator. |
| Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Baseline up to 28 days after last dose of study treatment, an average of 14 months | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity. Palbociclib-related TEAEs were determined by the investigator. |
| Number of Participants With Serious Adverse Events (All Causalities and Palbociclib-Related) | Baseline up to 28 days after last dose of study treatment, an average of 14 months | An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Palbociclib-related SAEs were determined by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Response and Partial Response | Baseline and per routine clinical practice to time of last dose of study treatment, an average of 1 year | Tumor response assessments were evaluated as per local guidelines by investigators and were collected in the CRF. No response confirmation was applied. |
| Change From Baseline in EQ-VAS Score | The descriptive analysis was carried out on Day 1 of each cycle (cycle 1 to cycle 38), at end of treatment (EOT) and end of study (EOS), up to 3 years. Cycle 1 Day 1 is taken to be baseline. | The EuroQol-5D (EQ-5D) (version 3L) consisted of 2 parts. The second part consisted of a visual analogue scale (the EuroQol-visual analogue scale \[EQ-VAS\]). The respondent's self-rated health was assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) |
| The Objective Response Rate (ORR) | Baseline and per routine clinical practice to time of last dose of study treatment, an average of 1 year | The tumor response was based on the response reported by investigator per local practice. No response confirmation was applied. ORR was defined as the percentage of participants with complete response or partial response relative to all as-treated population. |
| EQ-5D Health Utility Index Score | The descriptive analysis was carried out on Day 1 of each cycle (cycle 1 to cycle 38), at end of treatment (EOT) and end of study (EOS), up to 3 years. Cycle 1 Day 1 is taken to be baseline. | The EuroQol-5D (EQ-5D) (version 3L) consisted of 2 parts. The first part was a 5 item questionnaire designed to assess health status in terms of a single index value or utility score. It consisted of 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). A respondent was asked to rate each state on a three level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/impairment. The answers given to the 5 descriptors permit to find 243 unique health states which can be converted into a single EQ-5D index value by published algorithms. For the EQ-5D index, published weights are available that allow for the creation of a summary score ranging from -0.594 to 1, with low scores representing a higher level of dysfunction and 1 as perfect health. |
| Change From Baseline in EQ-5D Health Utility Index Score | The descriptive analysis was carried out on Day 1 of each cycle (cycle 1 to cycle 38), at end of treatment (EOT) and end of study (EOS), up to 3 years. Cycle 1 Day 1 is taken to be baseline. | The EuroQol-5D (EQ-5D) (version 3L) consisted of 2 parts. The first part was a 5 item questionnaire designed to assess health status in terms of a single index value or utility score. It consisted of 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). A respondent was asked to rate each state on a three level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/impairment. The answers given to the 5 descriptors permit to find 243 unique health states which can be converted into a single EQ-5D index value by published algorithms. For the EQ-5D index, published weights are available that allow for the creation of a summary score ranging from -0.594 to 1, with low scores representing a higher level of dysfunction and 1 as perfect health. |
| EQ-VAS Score | The descriptive analysis was carried out on Day 1 of each cycle (cycle 1 to cycle 38), at end of treatment (EOT) and end of study (EOS), up to 3 years. Cycle 1 Day 1 is taken to be baseline. | The EuroQol-5D (EQ-5D) (version 3L) consisted of 2 parts. The second part consisted of a visual analogue scale (the EuroQol-visual analogue scale \[EQ-VAS\]). The respondent's self-rated health was assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) |
Countries
Australia, India
Participant flow
Pre-assignment details
252 participants were assigned to treatment at 20 sites in India and Australia (100 in India, 152 in Australia)
Participants by arm
| Arm | Count |
|---|---|
| Palbociclib+Letrozole India Cohort Participants received Palbociclib orally once a day at 125 mg for 21 days followed by 7 days off treatment for each 28-day cycle. Participants received Letrozole orally at 2.5 mg once daily as continuous daily dosing schedule according to product labeling and in compliance with its local prescribing information | 100 |
| Palbociclib+Letrozole Australia Cohort Participants received Palbociclib orally once a day at 125 mg for 21 days followed by 7 days off treatment for each 28-day cycle. Participants received Letrozole orally at 2.5 mg once daily as continuous daily dosing schedule according to product labeling and in compliance with its local prescribing information | 152 |
| Total | 252 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 |
| Overall Study | Adverse events not related to study drug | 1 | 2 |
| Overall Study | Death | 0 | 3 |
| Overall Study | Global deterioration of health status | 1 | 8 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Not defined | 0 | 2 |
| Overall Study | Objective progression or relapse | 24 | 83 |
| Overall Study | Withdrawal by participant | 6 | 3 |
Baseline characteristics
| Characteristic | Palbociclib+Letrozole India Cohort | Palbociclib+Letrozole Australia Cohort | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 29 Participants | 45 Participants | 74 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants | 107 Participants | 178 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 100 Participants | 12 Participants | 112 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 9 Participants | 9 Participants |
| Race (NIH/OMB) White | 0 Participants | 130 Participants | 130 Participants |
| Sex: Female, Male Female | 100 Participants | 152 Participants | 252 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 100 | 7 / 152 |
| other Total, other adverse events | 85 / 100 | 151 / 152 |
| serious Total, serious adverse events | 18 / 100 | 45 / 152 |
Outcome results
Primary
Number of Participants With Serious Adverse Events (All Causalities and Palbociclib-Related)
An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Palbociclib-related SAEs were determined by the investigator.
Time frame: Baseline up to 28 days after last dose of study treatment, an average of 14 months
Population: The analysis population included all participants who received at least 1 dose of palbociclib treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Palbociclib+Letrozole India Cohort | Number of Participants With Serious Adverse Events (All Causalities and Palbociclib-Related) | All-causality | 18 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Serious Adverse Events (All Causalities and Palbociclib-Related) | Palciclib-Related | 8 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Serious Adverse Events (All Causalities and Palbociclib-Related) | All-causality | 45 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Serious Adverse Events (All Causalities and Palbociclib-Related) | Palciclib-Related | 12 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Serious Adverse Events (All Causalities and Palbociclib-Related) | All-causality | 63 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Serious Adverse Events (All Causalities and Palbociclib-Related) | Palciclib-Related | 20 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as treatment emergent adverse events (TEAEs). AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity. A serious adverse event (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.
Time frame: Baseline up to 28 days after last dose of study treatment, an average of 14 months
Population: The analysis population included all participants who received at least 1 dose of palbociclib treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants with grade 5 adverse events | 3 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants with grade 3 or 4 adverse events | 69 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants with adverse events | 92 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants with serious adverse events | 18 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants discontinued due to adverse events | 2 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants with grade 3 or 4 adverse events | 124 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants with adverse events | 152 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants with serious adverse events | 45 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants with grade 5 adverse events | 7 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants discontinued due to adverse events | 9 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants discontinued due to adverse events | 11 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants with grade 5 adverse events | 10 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants with adverse events | 244 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants with grade 3 or 4 adverse events | 193 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events (All Causalities) | Participants with serious adverse events | 63 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity.
Time frame: Baseline up to 28 days after last dose of study treatment, an average of 14 months
Population: The analysis population included all participants who received at least 1 dose of palbociclib treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 1 | 7 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 4 | 17 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 3 | 49 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 5 | 3 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 2 | 16 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 5 | 7 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 1 | 11 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 2 | 16 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 3 | 105 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 4 | 13 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 2 | 32 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 5 | 10 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 4 | 30 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 1 | 18 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events by Severity (All Causalities) | Grade 3 | 154 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity. Palbociclib-related TEAEs were determined by the investigator.
Time frame: Baseline up to 28 days after last dose of study treatment, an average of 14 months
Population: The analysis population included all participants who received at least 1 dose of palbociclib treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 4 | 15 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 3 | 49 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 1 | 6 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 2 | 10 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 5 | 0 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 3 | 93 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 1 | 21 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 2 | 14 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 4 | 14 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 5 | 1 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 5 | 1 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 4 | 29 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 1 | 27 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 3 | 142 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events by Severity (Palbociclib-Related) | Grade 2 | 24 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. All AEs reported after initiation of study drug treatment were considered as TEAE. AE severity was graded according to Common Terminology Criteria for AEs (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity. An 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. Palbociclib-related TEAEs were determined by the investigator.
Time frame: Baseline up to 28 days after last dose of study treatment, an average of 14 months
Population: The analysis population included all participants who received at least 1 dose of palbociclib treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants with grade 5 adverse events | 0 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants with grade 3 or 4 adverse events | 64 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants with adverse events | 80 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants with serious adverse events | 8 Participants |
| Palbociclib+Letrozole India Cohort | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants discontinued due to adverse events | 1 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants with grade 3 or 4 adverse events | 108 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants with adverse events | 143 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants with serious adverse events | 12 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants with grade 5 adverse events | 1 Participants |
| Palbociclib+Letrozole Australia Cohort | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants discontinued due to adverse events | 4 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants discontinued due to adverse events | 5 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants with grade 5 adverse events | 1 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants with adverse events | 223 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants with grade 3 or 4 adverse events | 172 Participants |
| Palbociclib+LetrozoleTotal | Number of Participants With Treatment-Emergent Adverse Events (Palbociclib-Related) | Participants with serious adverse events | 20 Participants |
Secondary
Change From Baseline in EQ-5D Health Utility Index Score
The EuroQol-5D (EQ-5D) (version 3L) consisted of 2 parts. The first part was a 5 item questionnaire designed to assess health status in terms of a single index value or utility score. It consisted of 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). A respondent was asked to rate each state on a three level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/impairment. The answers given to the 5 descriptors permit to find 243 unique health states which can be converted into a single EQ-5D index value by published algorithms. For the EQ-5D index, published weights are available that allow for the creation of a summary score ranging from -0.594 to 1, with low scores representing a higher level of dysfunction and 1 as perfect health.
Time frame: The descriptive analysis was carried out on Day 1 of each cycle (cycle 1 to cycle 38), at end of treatment (EOT) and end of study (EOS), up to 3 years. Cycle 1 Day 1 is taken to be baseline.
Population: PRO-evaluable population was only consisted of the Australia cohort
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Baseline (Cycle 1 Day 1) | 0.786 Scores on a scale | Standard Deviation 0.171 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 2 Day 1 | 0.013 Scores on a scale | Standard Deviation 0.172 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 3 Day 1 | 0.021 Scores on a scale | Standard Deviation 0.156 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 4 Day 1 | 0.052 Scores on a scale | Standard Deviation 0.175 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 5 Day 1 | 0.052 Scores on a scale | Standard Deviation 0.181 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 6 Day 1 | 0.037 Scores on a scale | Standard Deviation 0.214 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 7 Day 1 | 0.033 Scores on a scale | Standard Deviation 0.173 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 8 Day 1 | 0.050 Scores on a scale | Standard Deviation 0.156 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 9 Day 1 | 0.057 Scores on a scale | Standard Deviation 0.165 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 10 Day 1 | 0.049 Scores on a scale | Standard Deviation 0.192 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 11 Day 1 | 0.034 Scores on a scale | Standard Deviation 0.225 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 12 Day 1 | 0.029 Scores on a scale | Standard Deviation 0.235 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 13 Day 1 | 0.058 Scores on a scale | Standard Deviation 0.203 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 14 Day 1 | 0.058 Scores on a scale | Standard Deviation 0.188 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 15 Day 1 | 0.062 Scores on a scale | Standard Deviation 0.184 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 16 Day 1 | 0.051 Scores on a scale | Standard Deviation 0.182 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 17 Day 1 | 0.059 Scores on a scale | Standard Deviation 0.165 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 18 Day 1 | 0.060 Scores on a scale | Standard Deviation 0.181 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 19 Day 1 | 0.061 Scores on a scale | Standard Deviation 0.179 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 20 Day 1 | 0.069 Scores on a scale | Standard Deviation 0.197 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 21 Day 1 | 0.082 Scores on a scale | Standard Deviation 0.169 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 22 Day 1 | 0.076 Scores on a scale | Standard Deviation 0.081 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 23 Day 1 | 0.073 Scores on a scale | Standard Deviation 0.193 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 24 Day 1 | 0.085 Scores on a scale | Standard Deviation 0.183 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 25 Day 1 | 0.083 Scores on a scale | Standard Deviation 0.192 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 26 Day 1 | 0.052 Scores on a scale | Standard Deviation 0.14 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 27 Day 1 | 0.063 Scores on a scale | Standard Deviation 0.129 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 28 Day 1 | 0.071 Scores on a scale | Standard Deviation 0.153 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 29 Day 1 | 0.056 Scores on a scale | Standard Deviation 0.126 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 30 Day 1 | 0.055 Scores on a scale | Standard Deviation 0.122 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 31 Day 1 | -0.013 Scores on a scale | Standard Deviation 0.243 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 32 Day 1 | 0.049 Scores on a scale | Standard Deviation 0.099 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 33 Day 1 | 0.060 Scores on a scale | Standard Deviation 0.098 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 34 Day 1 | 0.026 Scores on a scale | Standard Deviation 0.123 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 35 Day 1 | 0.092 Scores on a scale | Standard Deviation 0.134 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 36 Day 1 | -0.036 Scores on a scale | Standard Deviation 0.24 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 37 Day 1 | 0.011 Scores on a scale | Standard Deviation 0.107 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | Cycle 38 Day 1 | -0.012 Scores on a scale | Standard Deviation 0.232 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | End of Treatment (EOT) | -0.147 Scores on a scale | Standard Deviation 0.239 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-5D Health Utility Index Score | End of Study (EOT) | -0.022 Scores on a scale | Standard Deviation 0.228 |
Secondary
Change From Baseline in EQ-VAS Score
The EuroQol-5D (EQ-5D) (version 3L) consisted of 2 parts. The second part consisted of a visual analogue scale (the EuroQol-visual analogue scale \[EQ-VAS\]). The respondent's self-rated health was assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state)
Time frame: The descriptive analysis was carried out on Day 1 of each cycle (cycle 1 to cycle 38), at end of treatment (EOT) and end of study (EOS), up to 3 years. Cycle 1 Day 1 is taken to be baseline.
Population: PRO-evaluable population was only consisted of the Australia cohort
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Baseline (Cycle 1 Day 1) | 76.9 Scores on a scale | Standard Deviation 16 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 2 Day 1 | 0.4 Scores on a scale | Standard Deviation 13.28 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 3 Day 1 | 0.3 Scores on a scale | Standard Deviation 13.47 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 4 Day 1 | 2.9 Scores on a scale | Standard Deviation 13.06 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 5 Day 1 | 3.2 Scores on a scale | Standard Deviation 14.7 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 6 Day 1 | 2.3 Scores on a scale | Standard Deviation 15.53 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 7 Day 1 | 2.0 Scores on a scale | Standard Deviation 15.79 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 8 Day 1 | 2.4 Scores on a scale | Standard Deviation 13.64 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 9 Day 1 | 2.3 Scores on a scale | Standard Deviation 12.54 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 10 Day 1 | 2.4 Scores on a scale | Standard Deviation 14.44 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 11 Day 1 | 2.1 Scores on a scale | Standard Deviation 13.72 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 12 Day 1 | 2.9 Scores on a scale | Standard Deviation 13.76 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 13 Day 1 | 2.1 Scores on a scale | Standard Deviation 13.84 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 14 Day 1 | 2.3 Scores on a scale | Standard Deviation 14 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 15 Day 1 | 3.5 Scores on a scale | Standard Deviation 12.12 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 16 Day 1 | 3.7 Scores on a scale | Standard Deviation 13.82 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 17 Day 1 | 3.9 Scores on a scale | Standard Deviation 12.77 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 18 Day 1 | 4.5 Scores on a scale | Standard Deviation 11.86 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 19 Day 1 | 4.6 Scores on a scale | Standard Deviation 11.69 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 20 Day 1 | 5.5 Scores on a scale | Standard Deviation 12.58 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 21 Day 1 | 6.0 Scores on a scale | Standard Deviation 11.77 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 22 Day 1 | 5.0 Scores on a scale | Standard Deviation 9.71 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 23 Day 1 | 4.4 Scores on a scale | Standard Deviation 13.2 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 24 Day 1 | 4.6 Scores on a scale | Standard Deviation 11.93 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 25 Day 1 | 4.3 Scores on a scale | Standard Deviation 10.71 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 26 Day 1 | 4.4 Scores on a scale | Standard Deviation 8.63 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 27 Day 1 | 5.6 Scores on a scale | Standard Deviation 6.26 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 28 Day 1 | 5.5 Scores on a scale | Standard Deviation 8.24 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 29 Day 1 | 5.9 Scores on a scale | Standard Deviation 7.57 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 30 Day 1 | 6.5 Scores on a scale | Standard Deviation 7.88 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 31 Day 1 | 4.3 Scores on a scale | Standard Deviation 11.52 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 32 Day 1 | 7.3 Scores on a scale | Standard Deviation 10.59 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 33 Day 1 | 7.1 Scores on a scale | Standard Deviation 12.75 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 34 Day 1 | 7.6 Scores on a scale | Standard Deviation 6.68 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 35 Day 1 | 6.6 Scores on a scale | Standard Deviation 9.27 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 36 Day 1 | 3.5 Scores on a scale | Standard Deviation 8.22 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 37 Day 1 | 10.3 Scores on a scale | Standard Deviation 1.71 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | Cycle 38 Day 1 | 9.0 Scores on a scale | Standard Deviation 4.24 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | End of Treatment (EOT) | -3.2 Scores on a scale | Standard Deviation 22.24 |
| Palbociclib+Letrozole Australia Cohort | Change From Baseline in EQ-VAS Score | End of Study (EOS) | 0.4 Scores on a scale | Standard Deviation 19.72 |
Secondary
EQ-5D Health Utility Index Score
The EuroQol-5D (EQ-5D) (version 3L) consisted of 2 parts. The first part was a 5 item questionnaire designed to assess health status in terms of a single index value or utility score. It consisted of 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). A respondent was asked to rate each state on a three level scale (1=no problem, 2=some problem, and 3=extreme problem) with higher levels indicating greater severity/impairment. The answers given to the 5 descriptors permit to find 243 unique health states which can be converted into a single EQ-5D index value by published algorithms. For the EQ-5D index, published weights are available that allow for the creation of a summary score ranging from -0.594 to 1, with low scores representing a higher level of dysfunction and 1 as perfect health.
Time frame: The descriptive analysis was carried out on Day 1 of each cycle (cycle 1 to cycle 38), at end of treatment (EOT) and end of study (EOS), up to 3 years. Cycle 1 Day 1 is taken to be baseline.
Population: Patient reported outcome (PRO)-evaluable population was only consisted of the Australia cohort
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 14 Day 1 | 0.842 Scores on a scale | Standard Deviation 0.159 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 1 Day 1 | 0.786 Scores on a scale | Standard Deviation 0.171 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 2 Day 1 | 0.798 Scores on a scale | Standard Deviation 0.187 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 3 Day 1 | 0.798 Scores on a scale | Standard Deviation 0.169 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 4 Day 1 | 0.836 Scores on a scale | Standard Deviation 0.172 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 5 Day 1 | 0.838 Scores on a scale | Standard Deviation 0.153 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 6 Day 1 | 0.825 Scores on a scale | Standard Deviation 0.185 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 7 Day 1 | 0.818 Scores on a scale | Standard Deviation 0.167 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 8 Day 1 | 0.831 Scores on a scale | Standard Deviation 0.169 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 9 Day 1 | 0.845 Scores on a scale | Standard Deviation 0.149 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 10 Day 1 | 0.840 Scores on a scale | Standard Deviation 0.162 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 11 Day 1 | 0.820 Scores on a scale | Standard Deviation 0.193 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 12 Day 1 | 0.810 Scores on a scale | Standard Deviation 0.188 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 13 Day 1 | 0.839 Scores on a scale | Standard Deviation 0.183 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 15 Day 1 | 0.840 Scores on a scale | Standard Deviation 0.138 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 16 Day 1 | 0.830 Scores on a scale | Standard Deviation 0.182 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 17 Day 1 | 0.837 Scores on a scale | Standard Deviation 0.163 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 18 Day 1 | 0.836 Scores on a scale | Standard Deviation 0.182 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 19 Day 1 | 0.848 Scores on a scale | Standard Deviation 0.179 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 20 Day 1 | 0.853 Scores on a scale | Standard Deviation 0.143 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 21 Day 1 | 0.868 Scores on a scale | Standard Deviation 0.132 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 22 Day 1 | 0.864 Scores on a scale | Standard Deviation 0.132 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 23 Day 1 | 0.846 Scores on a scale | Standard Deviation 0.17 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 24 Day 1 | 0.864 Scores on a scale | Standard Deviation 0.135 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 25 Day 1 | 0.861 Scores on a scale | Standard Deviation 0.138 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 26 Day 1 | 0.869 Scores on a scale | Standard Deviation 0.143 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 27 Day 1 | 0.884 Scores on a scale | Standard Deviation 0.14 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 28 Day 1 | 0.876 Scores on a scale | Standard Deviation 0.152 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 29 Day 1 | 0.852 Scores on a scale | Standard Deviation 0.147 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 30 Day 1 | 0.857 Scores on a scale | Standard Deviation 0.16 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 31 Day 1 | 0.784 Scores on a scale | Standard Deviation 0.278 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 32 Day 1 | 0.864 Scores on a scale | Standard Deviation 0.163 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 33 Day 1 | 0.870 Scores on a scale | Standard Deviation 0.14 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 34 Day 1 | 0.838 Scores on a scale | Standard Deviation 0.16 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 35 Day 1 | 0.905 Scores on a scale | Standard Deviation 0.128 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 36 Day 1 | 0.779 Scores on a scale | Standard Deviation 0.294 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 37 Day 1 | 0.854 Scores on a scale | Standard Deviation 0.17 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | Cycle 38 Day 1 | 0.810 Scores on a scale | Standard Deviation 0.269 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | End of Treatment (EOT) | 0.698 Scores on a scale | Standard Deviation 0.324 |
| Palbociclib+Letrozole Australia Cohort | EQ-5D Health Utility Index Score | End of Study (EOS) | 0.770 Scores on a scale | Standard Deviation 0.247 |
Secondary
EQ-VAS Score
The EuroQol-5D (EQ-5D) (version 3L) consisted of 2 parts. The second part consisted of a visual analogue scale (the EuroQol-visual analogue scale \[EQ-VAS\]). The respondent's self-rated health was assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state)
Time frame: The descriptive analysis was carried out on Day 1 of each cycle (cycle 1 to cycle 38), at end of treatment (EOT) and end of study (EOS), up to 3 years. Cycle 1 Day 1 is taken to be baseline.
Population: PRO-evaluable population was only consisted of the Australia cohort
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 18 Day 1 | 83.1 Scores on a scale | Standard Deviation 12.31 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 1 Day 1 | 76.9 Scores on a scale | Standard Deviation 16 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 2 Day 1 | 77.3 Scores on a scale | Standard Deviation 15.29 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 3 Day 1 | 77.4 Scores on a scale | Standard Deviation 15.52 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 4 Day 1 | 80.3 Scores on a scale | Standard Deviation 14.17 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 5 Day 1 | 80.4 Scores on a scale | Standard Deviation 14.66 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 6 Day 1 | 79.8 Scores on a scale | Standard Deviation 15.77 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 7 Day 1 | 79.7 Scores on a scale | Standard Deviation 14.81 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 8 Day 1 | 80.1 Scores on a scale | Standard Deviation 13.75 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 9 Day 1 | 80.9 Scores on a scale | Standard Deviation 14.54 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 10 Day 1 | 81.2 Scores on a scale | Standard Deviation 14.75 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 11 Day 1 | 81.0 Scores on a scale | Standard Deviation 14.6 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 12 Day 1 | 81.3 Scores on a scale | Standard Deviation 13.99 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 13 Day 1 | 80.4 Scores on a scale | Standard Deviation 14.37 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 14 Day 1 | 80.9 Scores on a scale | Standard Deviation 13.72 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 15 Day 1 | 82.1 Scores on a scale | Standard Deviation 12.24 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 16 Day 1 | 82.9 Scores on a scale | Standard Deviation 12.93 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 17 Day 1 | 83.1 Scores on a scale | Standard Deviation 12.89 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 19 Day 1 | 83.7 Scores on a scale | Standard Deviation 12.75 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 20 Day 1 | 84.5 Scores on a scale | Standard Deviation 12.1 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 21 Day 1 | 85.3 Scores on a scale | Standard Deviation 12.03 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 22 Day 1 | 85.5 Scores on a scale | Standard Deviation 11.77 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 23 Day 1 | 84.1 Scores on a scale | Standard Deviation 14.3 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 24 Day 1 | 85.6 Scores on a scale | Standard Deviation 12.78 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 25 Day 1 | 84.9 Scores on a scale | Standard Deviation 12.89 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 26 Day 1 | 87.6 Scores on a scale | Standard Deviation 11.08 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 27 Day 1 | 88.1 Scores on a scale | Standard Deviation 9.88 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 28 Day 1 | 87.5 Scores on a scale | Standard Deviation 9.32 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 29 Day 1 | 88.5 Scores on a scale | Standard Deviation 9.98 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 30 Day 1 | 91.5 Scores on a scale | Standard Deviation 6.97 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 31 Day 1 | 88.1 Scores on a scale | Standard Deviation 12.26 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 32 Day 1 | 91.0 Scores on a scale | Standard Deviation 8.06 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 33 Day 1 | 88.6 Scores on a scale | Standard Deviation 10.61 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 34 Day 1 | 91.0 Scores on a scale | Standard Deviation 8.06 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 35 Day 1 | 90.0 Scores on a scale | Standard Deviation 11 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 36 Day 1 | 87.5 Scores on a scale | Standard Deviation 14.84 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 37 Day 1 | 91.5 Scores on a scale | Standard Deviation 7.42 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | Cycle 38 Day 1 | 91.5 Scores on a scale | Standard Deviation 0.71 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | End of Treatment (EOT) | 73.6 Scores on a scale | Standard Deviation 23.88 |
| Palbociclib+Letrozole Australia Cohort | EQ-VAS Score | End of Study (EOS) | 77.3 Scores on a scale | Standard Deviation 18.99 |
Secondary
Percentage of Participants With Complete Response and Partial Response
Tumor response assessments were evaluated as per local guidelines by investigators and were collected in the CRF. No response confirmation was applied.
Time frame: Baseline and per routine clinical practice to time of last dose of study treatment, an average of 1 year
Population: The analysis population included participants with efficacy data contributing to the analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Palbociclib+Letrozole India Cohort | Percentage of Participants With Complete Response and Partial Response | Percentage of participants with complete response | 1.0 Percentage of evaluable participants |
| Palbociclib+Letrozole India Cohort | Percentage of Participants With Complete Response and Partial Response | Percentage of participants with partial response | 28.0 Percentage of evaluable participants |
| Palbociclib+Letrozole Australia Cohort | Percentage of Participants With Complete Response and Partial Response | Percentage of participants with complete response | 1.3 Percentage of evaluable participants |
| Palbociclib+Letrozole Australia Cohort | Percentage of Participants With Complete Response and Partial Response | Percentage of participants with partial response | 11.8 Percentage of evaluable participants |
| Palbociclib+LetrozoleTotal | Percentage of Participants With Complete Response and Partial Response | Percentage of participants with complete response | 1.2 Percentage of evaluable participants |
| Palbociclib+LetrozoleTotal | Percentage of Participants With Complete Response and Partial Response | Percentage of participants with partial response | 18.3 Percentage of evaluable participants |
Secondary
The Objective Response Rate (ORR)
The tumor response was based on the response reported by investigator per local practice. No response confirmation was applied. ORR was defined as the percentage of participants with complete response or partial response relative to all as-treated population.
Time frame: Baseline and per routine clinical practice to time of last dose of study treatment, an average of 1 year
Population: The analysis population included participants with efficacy data contributing to the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Palbociclib+Letrozole India Cohort | The Objective Response Rate (ORR) | 29.0 Percentage of evaluable participants |
| Palbociclib+Letrozole Australia Cohort | The Objective Response Rate (ORR) | 13.2 Percentage of evaluable participants |
| Palbociclib+LetrozoleTotal | The Objective Response Rate (ORR) | 19.4 Percentage of evaluable participants |