Breast Cancer
Conditions
Keywords
Everolimus, Exemestane, Capecitabine, locally advanced, metastatic, breast cancer, breast cancer positive for human epidermal growth factor receptor 2, HER2, HER2 positive, breast cancer progression, estrogen-receptor positive breast cancer, ER
Brief summary
This was a three-arm, randomized, open label, multi-center phase II study investigating the combination of everolimus (10mg daily) with exemestane (25mg daily) versus everolimus (10mg daily) versus capecitabine (1250mg/m2 twice daily for 14 days, 3-week cycle) in patients with estrogen-receptor positive, HER2 negative, advanced breast cancer after recurrence or progression on letrozole or anastrozole.
Detailed description
The reference therapy (control arm) used in the course of this trial was the combination arm of everolimus plus exemestane. The investigational therapies in the context of this study were everolimus monotherapy and capecitabine monotherapy. All treatments were taken orally until disease progression, intolerable toxicity or withdrawal of patient's informed consent. Patients were randomly assigned with equal allocation to one of the treatment arms: 1. Exemestane (25mg daily) in combination with everolimus (10mg daily) 2. Everolimus (10mg daily) 3. Capecitabine (1250mg/m2 twice daily) orally for two weeks, followed by a one week rest period in 3-weeks cycles. Treatment assignment was stratified by the presence of visceral disease (yes vs. no). Visceral refered to lung, liver, heart, ovary, spleen, kidney, adrenal gland, malignant pleural or pericardial effusion or malignant ascites. Randomization and Treatment Phase: At Visit 3 all eligible patients were randomized in 1:1:1 ratio to receive everolimus (10mg daily oral tablets) in combination with exemestane (25 mg daily oral tablets), everolimus (10mg daily oral tablets) or capecitabine monotherapy (1250mg/m2 twice daily orally for two weeks followed by a one week rest period in 3-weeks cycles). Assignment was stratified by the presence of visceral disease (yes vs. no). Visceral refered to lung, liver, heart, ovary, spleen, kidney, adrenal gland, malignant pleural or pericardial effusion or malignant ascites. After randomization, study treatment started and continued until progression, intolerable toxicity or consent withdrawal. Further treatment after progression and study treatment discontinuation was at the investigator's discretion. Dose adjustment (reduction, interruption) according to safety findings was allowed. Regular safety and efficacy reviews by Data Monitoring Committee (DMC) were performed. Tumor assessments were performed every 6 weeks until disease progression. Additional evaluation were performed to confirm response at 4 weeks after it was first observed. After at least 150 PFS events had been documented per RECIST 1.1 by local assessment in each of the two following groups: (i) everolimus + exemestane arm plus everolimus monotherapy arm, and (ii) everolimus + exemestane arm plus capecitabine monotherapy arm, the frequency of tumor assessments was changed to every 12 weeks or as clinically indicated. Follow-up phase: Patients were followed for safety for 30 days after study treatment discontinuation. If a patient did not discontinue study treatment due to disease progression, lost to follow-up or consent withdrawal, then tumor assessments continued to be performed every 6 weeks until disease progression, death, lost to follow-up or investigator decision in patient best interest. Survival Data Collection: All patients were followed for survival status at least every 3 months regardless of treatment discontinuation reason and up to two years after randomization of last patient. Survival information could be obtained via phone and information were documented in the source documents and eCRF. Additional survival follow-up might be performed more frequently if a survival update was required for reporting the results or to meet safety or regulatory needs.
Interventions
DRUGCapecitabine
Capecitabine, tablets for oral use, 1250 mg/m² twice daily for 2 weeks followed by one week rest (3-week-cycle) (locally supplied)
DRUGExemestane
Exemestane, tablets for oral use, 25 mg per day in (locally supplied)
DRUGEverolimus
Everolimus, 5 mg tablets for oral use, 10 mg (2 x 5 mg) per day (centrally supplied)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: \- Women with locally advanced, recurrent, or metastatic breast cancer along with confirmation of estrogen-receptor positive (ER+). Measurable disease defined as at least one lesion ≥ 10 mm by CT or MRI that can be accurately measured in at least one dimension (CT scan slice thickness ≤ 5 mm) OR • Bone lesions: lytic or mixed (lytic + blastic) in the absence of measurable disease as defined above. Key
Exclusion criteria
\- Patients who received more than one chemotherapy line. Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic) bone metastasis.Previous treatment with exemestane, mTOR inhibitors, PI3K inhibitors or AKT inhibitors.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Everolimus Alone | Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 39 months | Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. PFS was compared between the everolimus + exemestane combination therapy with the everolimus monotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Every 3 months following end of treatment visit, assessed for approximately 54 months | Overall Survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. |
| Overall Response Rate (ORR) | From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 43 months | Overall Response Rate (ORR) as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST 1.1 This was assessed in the full patient population. Complete response is achieved when all lesions evaluated at baseline are absent at subsequent visit. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Only descriptive statistics. |
| Clinical Benefit Rate (CBR) | From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 43 months | Clinical Benefit Rate (CBR) is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 24 weeks based on local investigator's assessment according to RECIST 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR, Stable disease (SD), neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; CBR = CR+PR+SD. Only descriptive statistics. |
| Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Capecitabine Alone | Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 39 months | Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. PFS was compared between the everolimus + exemestane combination therapy with the everolimus monotherapy. |
| Time to 10% Definitive Deterioration in the Global Health Status / Quality of Life | Baseline, every 6 weeks up to about 43 months | The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is the number of days between the date of randomization and the date of the assessment at which definitive deterioration is seen. Definitive 10% (5-point) deterioration is defined as a decrease in score by at least 10% (5-points) compared to baseline, with no later increase above this threshold observed during the course of the study. |
| Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Week 3, Week 12 | TSQM was used to measure the Patients' self-reported satisfaction or dissatisfaction with the study treatment. The differences in mean scale scores between weeks 3 and 12 comparing treatment satisfaction in the different treatment arms: everolimus + exemestane combination therapy versus everolimus monotherapy, and everolimus + exemestane combination therapy versus capecitabine monotherapy. The TSQM version 1.4 domain scores range from 0 to 100 with higher scores representing a higher satisfaction on that domain. |
| Time to Eastern Cooperative Oncology Group (ECOG) Performance Deterioration | Baseline, every 6 weeks up to about 43 months | The Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale used to assess physical health of subjects,ranging from 0 (most active) to 5 (least active). Definitive deterioration is defined as no improvement in the ECOG status following observation of the deterioration. |
Countries
Argentina, Australia, Belgium, Brazil, Denmark, Hungary, India, Ireland, Lebanon, Malaysia, Peru, Russia, Spain, Sweden, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 84 centers in 18 countries worldwide: Belgium (1), Denmark (6), Hungary (3), Ireland (3), Spain (4), Sweden (6), United Kingdom (3), United States (19), Argentina (6), Brazil (5), Peru (4), India (4), Lebanon (5), Malaysia (2), Russia (3), Thailand (3), Turkey (3) Australia (4)
Pre-assignment details
A total of 300 subjects were planned and total of 309 subjects were randomized to everolimus plus exemestane (control arm) (N = 104), everolimus alone (N = 103), or capecitabine (N = 102).
Participants by arm
| Arm | Count |
|---|---|
| Everolimus 10 mg + Exemestane 25 mg Everolimus (10 mg daily) with Exemestane (25 mg daily) (control arm). | 104 |
| Everolimus 10 mg Everolimus (10 mg daily) (investigational arm). | 103 |
| Capecitabine 1250 mg/m2 Capecitabine (1250 mg/m2 twice daily) for two weeks, followed by one week rest period in 3-weeks cycles (investigational arm). | 102 |
| Total | 309 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Post-Treatment Efficacy Follow-Up Phase | Administrative Problems | 0 | 1 | 0 |
| Post-Treatment Efficacy Follow-Up Phase | Death | 9 | 7 | 5 |
| Post-Treatment Efficacy Follow-Up Phase | Disease Progression | 7 | 8 | 11 |
| Post-Treatment Efficacy Follow-Up Phase | Followup phase completed as per protocol | 69 | 53 | 52 |
| Post-Treatment Efficacy Follow-Up Phase | New cancer therapy | 7 | 16 | 15 |
| Post-Treatment Efficacy Follow-Up Phase | Withdrawal by Subject | 4 | 8 | 8 |
| Treatment Phase | Administrative problems | 2 | 0 | 1 |
| Treatment Phase | Adverse Event | 9 | 20 | 19 |
| Treatment Phase | Death | 2 | 2 | 2 |
| Treatment Phase | Disease Progression | 76 | 66 | 64 |
| Treatment Phase | Physician Decision | 8 | 6 | 5 |
| Treatment Phase | Protocol Violation | 1 | 1 | 2 |
| Treatment Phase | Withdrawal by Subject | 6 | 8 | 9 |
Baseline characteristics
| Characteristic | Total | Capecitabine 1250 mg/m2 | Everolimus 10 mg | Everolimus 10 mg + Exemestane 25 mg |
|---|---|---|---|---|
| Age, Continuous | 60.6 Years STANDARD_DEVIATION 10.03 | 59.7 Years STANDARD_DEVIATION 10.5 | 61.3 Years STANDARD_DEVIATION 9.08 | 60.9 Years STANDARD_DEVIATION 10.47 |
| ECOG Performance Status Missing | 7 Participants | 2 Participants | 2 Participants | 3 Participants |
| ECOG Performance Status No Restrictions | 159 Participants | 57 Participants | 48 Participants | 54 Participants |
| ECOG Performance Status Only Light Work | 131 Participants | 39 Participants | 50 Participants | 42 Participants |
| ECOG Performance Status Only Self Care | 12 Participants | 4 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 27 Participants | 8 Participants | 8 Participants | 11 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 254 Participants | 91 Participants | 85 Participants | 78 Participants |
| Race/Ethnicity, Customized Native American | 5 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 20 Participants | 3 Participants | 6 Participants | 11 Participants |
| Sex: Female, Male Female | 309 Participants | 102 Participants | 103 Participants | 104 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 104 | 5 / 103 | 2 / 102 |
| other Total, other adverse events | 103 / 104 | 100 / 103 | 99 / 102 |
| serious Total, serious adverse events | 37 / 104 | 30 / 103 | 30 / 102 |
Outcome results
Primary
Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Everolimus Alone
Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. PFS was compared between the everolimus + exemestane combination therapy with the everolimus monotherapy.
Time frame: Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 39 months
Population: Full Analysis Set (FAS), which consisted of all randomized patients, was considered.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Everolimus 10 mg + Exemestane 25 mg | Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Everolimus Alone | 8.41 Months |
| Everolimus 10 mg | Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Everolimus Alone | 6.77 Months |
90% CI: [0.57, 0.97]
Secondary
Clinical Benefit Rate (CBR)
Clinical Benefit Rate (CBR) is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 24 weeks based on local investigator's assessment according to RECIST 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR, Stable disease (SD), neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; CBR = CR+PR+SD. Only descriptive statistics.
Time frame: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 43 months
Population: Full Analysis Set (FAS), which consisted of all randomized patients, was considered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus 10 mg + Exemestane 25 mg | Clinical Benefit Rate (CBR) | 59 Percentage of Participants |
| Everolimus 10 mg | Clinical Benefit Rate (CBR) | 43 Percentage of Participants |
| Capecitabine 1250 mg/m2 | Clinical Benefit Rate (CBR) | 53 Percentage of Participants |
Secondary
Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12
TSQM was used to measure the Patients' self-reported satisfaction or dissatisfaction with the study treatment. The differences in mean scale scores between weeks 3 and 12 comparing treatment satisfaction in the different treatment arms: everolimus + exemestane combination therapy versus everolimus monotherapy, and everolimus + exemestane combination therapy versus capecitabine monotherapy. The TSQM version 1.4 domain scores range from 0 to 100 with higher scores representing a higher satisfaction on that domain.
Time frame: Week 3, Week 12
Population: Full Analysis Set (FAS), which consisted of all randomized patients, was considered. Only participants who had both post-baseline assessments were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Everolimus 10 mg + Exemestane 25 mg | Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Side-effects | -4.8 Unit on a scale | Standard Deviation 28.88 |
| Everolimus 10 mg + Exemestane 25 mg | Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Effectiveness | -2.2 Unit on a scale | Standard Deviation 20.15 |
| Everolimus 10 mg + Exemestane 25 mg | Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Convenience | -0.6 Unit on a scale | Standard Deviation 12 |
| Everolimus 10 mg + Exemestane 25 mg | Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Global satisfaction | -1.0 Unit on a scale | Standard Deviation 17.32 |
| Everolimus 10 mg | Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Global satisfaction | 1.8 Unit on a scale | Standard Deviation 20.8 |
| Everolimus 10 mg | Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Side-effects | -9.1 Unit on a scale | Standard Deviation 21.88 |
| Everolimus 10 mg | Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Convenience | 1.0 Unit on a scale | Standard Deviation 16.41 |
| Everolimus 10 mg | Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Effectiveness | 1.2 Unit on a scale | Standard Deviation 26.51 |
| Capecitabine 1250 mg/m2 | Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Global satisfaction | 2.3 Unit on a scale | Standard Deviation 16.96 |
| Capecitabine 1250 mg/m2 | Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Effectiveness | 1.2 Unit on a scale | Standard Deviation 21.61 |
| Capecitabine 1250 mg/m2 | Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Convenience | 0.5 Unit on a scale | Standard Deviation 17.67 |
| Capecitabine 1250 mg/m2 | Mean Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Between Week 3 and 12 | Side-effects | -2.6 Unit on a scale | Standard Deviation 22.45 |
Comparison: Side-effects90% CI: [-3.3, 11.9]
Comparison: Side-effects90% CI: [-9.9, 5.5]
Comparison: Effectiveness90% CI: [-10.4, 3.8]
Comparison: Effectiveness90% CI: [-9.7, 3]
Comparison: Convenience90% CI: [-5.8, 2.5]
Comparison: Convenience90% CI: [-5.5, 3.3]
Comparison: Global Satisfaction90% CI: [-8.3, 2.9]
Comparison: Global Satisfaction90% CI: [-8.4, 1.9]
Secondary
Overall Response Rate (ORR)
Overall Response Rate (ORR) as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST 1.1 This was assessed in the full patient population. Complete response is achieved when all lesions evaluated at baseline are absent at subsequent visit. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Only descriptive statistics.
Time frame: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 43 months
Population: Full Analysis Set (FAS), which consisted of all randomized patients, was considered.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Everolimus 10 mg + Exemestane 25 mg | Overall Response Rate (ORR) | 21 Percentage of Participants |
| Everolimus 10 mg | Overall Response Rate (ORR) | 12 Percentage of Participants |
| Capecitabine 1250 mg/m2 | Overall Response Rate (ORR) | 23 Percentage of Participants |
Secondary
Overall Survival (OS)
Overall Survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive.
Time frame: Every 3 months following end of treatment visit, assessed for approximately 54 months
Population: Full Analysis Set (FAS), which consisted of all randomized patients, was considered.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Everolimus 10 mg + Exemestane 25 mg | Overall Survival (OS) | 23.06 Months |
| Everolimus 10 mg | Overall Survival (OS) | 29.27 Months |
| Capecitabine 1250 mg/m2 | Overall Survival (OS) | 25.56 Months |
90% CI: [0.95, 1.7]
90% CI: [0.99, 1.79]
Secondary
Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Capecitabine Alone
Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. PFS was compared between the everolimus + exemestane combination therapy with the everolimus monotherapy.
Time frame: Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 39 months
Population: Full Analysis Set (FAS), which consisted of all randomized patients, was considered.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Everolimus 10 mg + Exemestane 25 mg | Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Capecitabine Alone | 8.41 Months |
| Everolimus 10 mg | Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Capecitabine Alone | 9.59 Months |
90% CI: [0.96, 1.66]
Secondary
Time to 10% Definitive Deterioration in the Global Health Status / Quality of Life
The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is the number of days between the date of randomization and the date of the assessment at which definitive deterioration is seen. Definitive 10% (5-point) deterioration is defined as a decrease in score by at least 10% (5-points) compared to baseline, with no later increase above this threshold observed during the course of the study.
Time frame: Baseline, every 6 weeks up to about 43 months
Population: Full Analysis Set (FAS), which consisted of all randomized patients, was considered.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Everolimus 10 mg + Exemestane 25 mg | Time to 10% Definitive Deterioration in the Global Health Status / Quality of Life | 30.86 Weeks |
| Everolimus 10 mg | Time to 10% Definitive Deterioration in the Global Health Status / Quality of Life | 23.86 Weeks |
| Capecitabine 1250 mg/m2 | Time to 10% Definitive Deterioration in the Global Health Status / Quality of Life | 61.29 Weeks |
90% CI: [0.46, 0.88]
90% CI: [0.93, 1.91]
Secondary
Time to Eastern Cooperative Oncology Group (ECOG) Performance Deterioration
The Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale used to assess physical health of subjects,ranging from 0 (most active) to 5 (least active). Definitive deterioration is defined as no improvement in the ECOG status following observation of the deterioration.
Time frame: Baseline, every 6 weeks up to about 43 months
Population: Full Analysis Set (FAS), which consisted of all randomized patients, was considered.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Everolimus 10 mg + Exemestane 25 mg | Time to Eastern Cooperative Oncology Group (ECOG) Performance Deterioration | 72.57 Weeks |
| Everolimus 10 mg | Time to Eastern Cooperative Oncology Group (ECOG) Performance Deterioration | 126.57 Weeks |
| Capecitabine 1250 mg/m2 | Time to Eastern Cooperative Oncology Group (ECOG) Performance Deterioration | 120.00 Weeks |
90% CI: [0.72, 1.66]
90% CI: [0.78, 1.77]
Post Hoc
All Collected Deaths
On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 224 weeks (treatment duration ranged from 1.3 to 220.0 weeks). Deaths post treatment survival follow up were collected after the on- treatment period, up to approximately 5 years. Patients who didn't die during the on-treatment period and had not stopped study participation at the time of data cut-off (end of study) were censored.
Time frame: up to 224 weeks (on-treatment), up to approximately 5 years (study duration)
Population: Clinical database population; all treated patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Everolimus 10 mg + Exemestane 25 mg | All Collected Deaths | Post-treatment deaths | 62 Participants |
| Everolimus 10 mg + Exemestane 25 mg | All Collected Deaths | On-treatment deaths | 9 Participants |
| Everolimus 10 mg + Exemestane 25 mg | All Collected Deaths | All deaths | 71 Participants |
| Everolimus 10 mg | All Collected Deaths | Post-treatment deaths | 55 Participants |
| Everolimus 10 mg | All Collected Deaths | On-treatment deaths | 5 Participants |
| Everolimus 10 mg | All Collected Deaths | All deaths | 60 Participants |
| Capecitabine 1250 mg/m2 | All Collected Deaths | On-treatment deaths | 2 Participants |
| Capecitabine 1250 mg/m2 | All Collected Deaths | All deaths | 59 Participants |
| Capecitabine 1250 mg/m2 | All Collected Deaths | Post-treatment deaths | 57 Participants |