Locally Advanced (Inoperable) or Metastatic Breast Cancer
Conditions
Keywords
Locally advanced (inoperable) or Metastatic Breast Cancer
Brief summary
Phase III, double-blind, randomised study assessing the efficacy of capivasertib + fulvestrant vs placebo + fulvestrant for the treatment of patients with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer following recurrence or progression on or after AI therapy.
Detailed description
Phase III, double-blind, randomised study assessing the efficacy of capivasertib + fulvestrant vs placebo + fulvestrant for the treatment of patients with locally advanced (inoperable) or metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) breast cancer following recurrence or progression on or after aromatase inhibitor (AI) therapy.
Interventions
DRUGFulvestrant
Patients will be administered 500 mg (2 injections) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter
DRUGCapivasertib
400 mg BD (2 tablets of 200 mg taken twice a day = total daily dose 800 mg) given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle
DRUGPlacebo
Placebo to match 400 mg BD (2 tablets of placebo to match 200 mg taken twice daily = placebo to match total daily dose of 800 mg) given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Double-blind Randomised Study
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
1. Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with an LHRH agonist. Patients are to have commenced concomitant treatment with LHRH agonist prior to or on Cycle 1, Day 1 and must be willing to continue on it for the duration of the study 2. Histologically confirmed HR+/HER2- breast cancer determined from the most recent tumour sample (primary or metastatic), as per the American Society of Clinical Oncology and College of American Pathologists guideline recommendations. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor. 3. Metastatic or locally advanced disease with radiological or objective evidence of recurrence or progression (the cancer should have shown progression during or after most recent therapy); locally advanced disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible) 4. ECOG/WHO PS: 0-1 5. Patients are to have received treatment with an AI (aromatase inhibitor) containing regimen (single agent or in combination) and have: 1. Radiological evidence of breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an AI, OR 2. Radiological evidence of progression while on prior AI administered as a treatment line for locally advanced or metastatic breast cancer (this does not need to be the most recent therapy) 6. Patients must have measurable disease according to RECIST 1.1 and/or at least 1 lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by CT or MRI; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible 7. FFPE tumour sample from primary/recurrent cancer for central testing
Exclusion criteria
1. Symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgement 2. More than 2 lines of endocrine therapy for inoperable locally advanced or metastatic disease 3. More than 1 line of chemotherapy for inoperable locally advanced or metastatic disease. Adjuvant and neoadjuvant chemotherapy are not classed as lines of chemotherapy for advanced breast cancer 4. Prior treatment with any of the following: 1. AKT, PI3K and mTOR inhibitors 2. Fulvestrant, and other SERDs 3. Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents within 3 weeks prior to study treatment initiation. 4. Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort) or drugs that are sensitive to CYP3A4 inhibition within 1 week prior to study treatment initiation. 5. Radiotherapy with a wide field of radiation up to 4 weeks before study treatment initiation (capivasertib/placebo) and/or radiotherapy with a limited field of radiation for palliation up to 2 weeks before study treatment initiation (capivasertib/placebo) 6. With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment 7. Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids up to 4 weeks before study treatment initiation 8. Any of the following cardiac criteria: 1. Mean resting QT interval corrected by Fridericia's formula (QTcF) \>470 msec obtained from 3 consecutive ECGs 2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block) 3. Any factors that increase the risk of corrected QT interval (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval 4. Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥2 5. Uncontrolled hypotension - systolic blood pressure \<90 mmHg and/or diastolic blood pressure \<50 mmHg 6. Cardiac ejection fraction outside institutional range of normal or \<50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition \[MUGA\] scan if an echocardiogram cannot be performed or is inconclusive) 9. Clinically significant abnormalities of glucose metabolism as defined by any of the following: 1. Patients with diabetes mellitus type 1 or diabetes mellitus type 2 requiring insulin treatment 2. HbA1c ≥8.0% (63.9 mmol/mol) 10. Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or LHRH agonist (if applicable) 11. Currently pregnant (confirmed with positive pregnancy test) or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival: Overall Population (Months) in the Global Cohort | Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression. | Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause, in the global cohort. Participants who discontinue treatment prior to progression should continue to be scanned until progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). |
| Progression Free Survival: Overall Population (Percentage) in the Global Cohort | Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression. | Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. Kaplan-Meier estimate was used. |
| Progression Free Survival: Altered Population (Months) in the Global Cohort | Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks. | Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. |
| Progression Free Survival: Altered Population (Percentage) in the Global Cohort | Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks. | Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Kaplan-Meier estimate was used. |
| Progression Free Survival: Overall Population (Months) in the China Cohort | Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression. | Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause, in the global cohort. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. |
| Progression Free Survival: Overall Population (Percentage) in the China Cohort | Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression. | Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. Kaplan-Meier estimate was used. |
| Progression Free Survival: Altered Population (Months) in the China Cohort | Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks. | Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. |
| Progression Free Survival: Altered Population (Percentage) in the China Cohort | Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks. | Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause Kaplan-Meier estimate was used. |
Countries
Argentina, Australia, Belgium, Canada, China, France, Germany, Hungary, Israel, Italy, Japan, Peru, Poland, Russia, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
A total of 708 participants in Global cohort (out of 818 participants in Global and China cohorts) were randomized to treatment. An additional 110 participants were enrolled into the China cohort only.
Pre-assignment details
A total of 818 participants were enrolled in the study. However, 24 participants were in both the Global and China cohorts.
Participants by arm
| Arm | Count |
|---|---|
| Capivasertib + Fulvestrant (Global + China Cohort) Capivasertib: 400 mg twice daily (2 tablets of 200 mg taken orally twice daily; total daily dose 800 mg) given on an intermittent weekly dosing schedule (4 days on/3 days off).
Fulvestrant: 500 mg (2 intramuscular injections of 250 mg/5 mL solution) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter. | 410 |
| Placebo + Fulvestrant (Global Cohort + China Cohort ) Placebo: Placebo tablets matching capivasertib. 400 mg twice daily (2 tablets of 200 mg taken orally twice daily; total daily dose 800 mg) given on an intermittent weekly dosing schedule (4 days on/3 days off).
Fulvestrant: 500 mg (2 intramuscular injections of 250 mg/5 mL solution) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter. | 408 |
| Total | 818 |
Baseline characteristics
| Characteristic | Capivasertib + Fulvestrant (Global + China Cohort) | Placebo + Fulvestrant (Global Cohort + China Cohort ) | Total |
|---|---|---|---|
| Age, Continuous China cohort | 54.7 years STANDARD_DEVIATION 10.66 | 55.0 years STANDARD_DEVIATION 10.6 | 54.8 years STANDARD_DEVIATION 10.59 |
| Age, Continuous Global cohort | 58.6 years STANDARD_DEVIATION 11.25 | 57.4 years STANDARD_DEVIATION 11.91 | 58.0 years STANDARD_DEVIATION 11.59 |
| Age, Customized China cohort >=50-<65 years | 39 Participants | 21 Participants | 60 Participants |
| Age, Customized China cohort <50 years | 19 Participants | 24 Participants | 43 Participants |
| Age, Customized China cohort >=65-<75 years | 12 Participants | 18 Participants | 30 Participants |
| Age, Customized China cohort >=75 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Customized Global cohort >=50-<65 years | 164 Participants | 152 Participants | 316 Participants |
| Age, Customized Global cohort <50 years | 76 Participants | 99 Participants | 175 Participants |
| Age, Customized Global cohort >=65-<75 years | 91 Participants | 76 Participants | 167 Participants |
| Age, Customized Global cohort >=75 years | 24 Participants | 26 Participants | 50 Participants |
| Ethnicity (NIH/OMB) China cohort Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) China cohort Not Hispanic or Latino | 69 Participants | 61 Participants | 130 Participants |
| Ethnicity (NIH/OMB) China cohort Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Global cohort Hispanic or Latino | 31 Participants | 31 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Global cohort Not Hispanic or Latino | 323 Participants | 322 Participants | 645 Participants |
| Ethnicity (NIH/OMB) Global cohort Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) China cohort American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) China cohort Asian | 69 Participants | 61 Participants | 130 Participants |
| Race (NIH/OMB) China cohort Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) China cohort More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) China cohort Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) China cohort Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) China cohort White | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Global cohort American Indian or Alaska Native | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Global cohort Asian | 95 Participants | 94 Participants | 189 Participants |
| Race (NIH/OMB) Global cohort Black or African American | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) Global cohort More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Global cohort Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Global cohort Unknown or Not Reported | 52 Participants | 47 Participants | 99 Participants |
| Race (NIH/OMB) Global cohort White | 201 Participants | 206 Participants | 407 Participants |
| Sex: Female, Male China cohort Female | 71 Participants | 62 Participants | 133 Participants |
| Sex: Female, Male China cohort Male | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Global cohort Female | 352 Participants | 349 Participants | 701 Participants |
| Sex: Female, Male Global cohort Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 355 | 1 / 350 | 1 / 71 | 0 / 62 |
| other Total, other adverse events | 334 / 355 | 255 / 350 | 67 / 71 | 52 / 62 |
| serious Total, serious adverse events | 57 / 355 | 28 / 350 | 20 / 71 | 3 / 62 |
Outcome results
Primary
Progression Free Survival: Altered Population (Months) in the China Cohort
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause.
Time frame: Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Population: Altered subgroup full analysis set in the China cohort
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Months) in the China Cohort | 5.7 Months |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Months) in the China Cohort | 1.9 Months |
p-value: 0.01695% CI: [0.19, 0.85]Stratified log rank test
Primary
Progression Free Survival: Altered Population (Months) in the Global Cohort
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause.
Time frame: Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Population: Altered population in the Global Cohort
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Months) in the Global Cohort | 7.3 Months |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Months) in the Global Cohort | 3.1 Months |
p-value: <0.00195% CI: [0.38, 0.65]Stratified log-rank test
Primary
Progression Free Survival: Altered Population (Percentage) in the China Cohort
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause Kaplan-Meier estimate was used.
Time frame: Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Population: Altered subgroup full analysis set in the China cohort
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Percentage) in the China Cohort | PFS rate at 6 months | 46.3 Percentage of participants |
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Percentage) in the China Cohort | PFS rate at 9 months | 23.1 Percentage of participants |
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Percentage) in the China Cohort | PFS rate at 12 months | 6.9 Percentage of participants |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Percentage) in the China Cohort | PFS rate at 6 months | 14.3 Percentage of participants |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Percentage) in the China Cohort | PFS rate at 9 months | 14.3 Percentage of participants |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Percentage) in the China Cohort | PFS rate at 12 months | 14.3 Percentage of participants |
p-value: 0.01695% CI: [0.19, 0.85]Stratified log rank test
Primary
Progression Free Survival: Altered Population (Percentage) in the Global Cohort
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Kaplan-Meier estimate was used.
Time frame: Assessed every 8 weeks for the first 2 years following objective disease progression or treatment discontinuation and then every 12 weeks.
Population: Altered population in the Global Cohort
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Percentage) in the Global Cohort | PFS rate at 6 months | 53.4 Percentage of participants |
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Percentage) in the Global Cohort | PFS rate at 9 months | 42.0 Percentage of participants |
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Percentage) in the Global Cohort | PFS rate at 12 months | 28.2 Percentage of participants |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Percentage) in the Global Cohort | PFS rate at 6 months | 29.6 Percentage of participants |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Percentage) in the Global Cohort | PFS rate at 9 months | 21.6 Percentage of participants |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Altered Population (Percentage) in the Global Cohort | PFS rate at 12 months | 15.8 Percentage of participants |
p-value: <0.00195% CI: [0.38, 0.65]Stratified log-rank test
Primary
Progression Free Survival: Overall Population (Months) in the China Cohort
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause, in the global cohort. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression.
Time frame: Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Population: Full analysis set in the China cohort
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Months) in the China Cohort | 6.9 Months |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Months) in the China Cohort | 2.8 Months |
p-value: <0.00195% CI: [0.34, 0.76]Stratified log rank test
Primary
Progression Free Survival: Overall Population (Months) in the Global Cohort
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause, in the global cohort. Participants who discontinue treatment prior to progression should continue to be scanned until progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s).
Time frame: Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Population: Overall population in the global cohort
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Months) in the Global Cohort | 7.2 Months |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Months) in the Global Cohort | 3.6 Months |
p-value: <0.00195% CI: [0.51, 0.71]Stratified log rank test
Primary
Progression Free Survival: Overall Population (Percentage) in the China Cohort
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. Kaplan-Meier estimate was used.
Time frame: Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Population: Full analysis set in the China cohort
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Percentage) in the China Cohort | PFS rate at 6 months | 53.9 Percentage of participants |
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Percentage) in the China Cohort | PFS rate at 9 months | 40.9 Percentage of participants |
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Percentage) in the China Cohort | PFS rate at 12 months | 29.6 Percentage of participants |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Percentage) in the China Cohort | PFS rate at 6 months | 24.5 Percentage of participants |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Percentage) in the China Cohort | PFS rate at 9 months | 24.5 Percentage of participants |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Percentage) in the China Cohort | PFS rate at 12 months | 19.1 Percentage of participants |
p-value: <0.00195% CI: [0.34, 0.76]Stratified log rank test
Primary
Progression Free Survival: Overall Population (Percentage) in the Global Cohort
Progression free survival (PFS), defined as the time from randomization until progression per RECIST v1.1, as assessed by the investigator at the local site, or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the longest diameter of target lesions (short axis diameter used for lymph nodes), or clinically significant increase in a non-target lesion, or the appearance of a new lesion(s). Participants who discontinue treatment prior to progression should continue to be scanned until progression. Kaplan-Meier estimate was used.
Time frame: Assessed every 8 weeks for the first 18 months and every 12 weeks thereafter, from randomization to radiological progression.
Population: Overall population in the Global Cohort
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Percentage) in the Global Cohort | PFS rate at 6 months | 51.8 Percentage of participants |
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Percentage) in the Global Cohort | PFS rate at 9 months | 40.9 Percentage of participants |
| Capivasertib + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Percentage) in the Global Cohort | PFS rate at 12 months | 28.5 Percentage of participants |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Percentage) in the Global Cohort | PFS rate at 6 months | 32.0 Percentage of participants |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Percentage) in the Global Cohort | PFS rate at 9 months | 24.4 Percentage of participants |
| Placebo + Fulvestrant (Global + China Cohort) | Progression Free Survival: Overall Population (Percentage) in the Global Cohort | PFS rate at 12 months | 18.4 Percentage of participants |
p-value: <0.00195% CI: [0.51, 0.71]Stratified log rank test