Advanced Ovarian Cancer, BRCA Mutation, Complete Response, FIGO Stage III-IV, First Line Platinum Chemotherapy, Newly Diagnosed, Partial Response
Conditions
Keywords
BRCA, Ovarian Cancer, Chemotherapy, PARP inhibitor, First Line, FIGO Stage III, FIGO Stage IV
Brief summary
Olaparib Monotherapy in Patients with BRCA Mutated Ovarian Cancer following First Line Platinum Based Chemotherapy.
Detailed description
A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib Maintenance Monotherapy in Patients with BRCA Mutated Advanced (FIGO Stage III-IV) Ovarian Cancer following First Line Platinum Based Chemotherapy.
Interventions
Olaparib/placebo tablets p.o 300mg twice daily for up to 2 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.
Sponsors
GOG Foundation
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme LLC
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Female patients with newly diagnosed, histologically confirmed, high risk advanced (FIGO stage III - IV) BRCA mutated high grade serous or high grade endometrioid ovarian cancer, primary peritoneal cancer and / or fallopian - tube cancer who have completed first line platinum based chemotherapy (intravenous or intraperitoneal). * Stage III patients must have had one attempt at optimal debulking surgery (upfront or interval debulking). Stage IV patients must have had either a biopsy and/or upfront or interval debulking surgery. * Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). * Patients who have completed first line platinum (e.g. carboplatin or cisplatin), containing therapy (intravenous or intraperitoneal) prior to randomisation: * Patients must have, in the opinion of the investigator, clinical complete response or partial response and have no clinical evidence of disease progression on the post treatment scan or rising CA-125 level, following completion of this chemotherapy course. Patients with stable disease on the post-treatment scan at completion of first line platinum-containing therapy are not eligible for the study. * Patients must be randomized within 8 weeks of their last dose of chemotherapy
Exclusion criteria
* BRCA1 and/or BRCA2 mutations that are considered to be non detrimental (e.g. Variants of uncertain clinical significance or Variant of unknown significance or Variant, favor polymorphism or benign polymorphism etc). * Patients with early stage disease (FIGO Stage I, IIA, IIB or IIC) * Stable disease or progressive disease on the post-treatment scan or clinical evidence of progression at the end of the patient's first line chemotherapy treatment. * Patients where more than one debulking surgery has been performed before randomisation to the study. (Patients who, at the time of diagnosis, are deemed to be unresectable and undergo only a biopsy or oophorectomy but then go on to receive chemotherapy and interval debulking surgery are eligible). * Patients who have previously been diagnosed and treated for earlier stage ovarian, fallopian tube or primary peritoneal cancer. * Patients who have previously received chemotherapy for any abdominal or pelvic tumour, including treatment for prior diagnosis at an earlier stage for their ovarian, fallopian tube or primary peritoneal cancer. (Patients who have received prior adjuvant chemotherapy for localised breast cancer may be eligible, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease). * Patients with synchronous primary endometrial cancer unless both of the following criteria are met: 1) stage \<2 2) less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade 3 endometrioid adenocarcinoma OR ≥ 60 years old at the time of diagnosis of endometrial cancer with Stage IA grade 1 or 2 endometrioid adenocarcinoma. Patients with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium are not eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) | Radiologic scans performed at baseline then every 12 weeks up to 156 weeks, then every 24 weeks thereafter until objective radiological disease progression. DCO: 17 May 2018 | To determine the efficacy by progression free survival (PFS) using investigator assessment according to modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death | CA-125 performed at baseline + every 4 weeks. Radiologic scans performed at baseline + every 12 weeks up to 156 weeks, then every 24 weeks until objective radiological disease progression. DCO:17May2018 | To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen-125 (CA-125) or death |
| Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression | Following first progression disease then assessed per local practice every 12 weeks until second progression. | To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to second progression (PFS2) |
| Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) | Questionnaires will be given to the patient at baseline, at Day 29 and then every 12 weeks for 156 weeks, then every 24 weeks or until the data cut off for the PFS analysis, change in TOI over 24 months reported | To compare the effects of olaparib maintenance monotherapy compared to placebo on Health-related Quality of Life (HRQoL) as assessed by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy. The TOI ranges from 0-100 and a higher score indicates a higher HRQoL. |
| Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival | Assessed every 4 weeks until treatment discontinues (up to a max of 156 weeks), then as per protocol. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity. | To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of overall survival (OS). Reports results of a pre-specified interim analysis; results for final OS analysis (235 OS events) anticipated 2029. |
| Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Second Subsequent Therapy or Death (TSST) | Assessed every 12 weeks following treatment discontinuation. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity. | To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to second subsequent therapy or death (TSST). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029). |
| Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Study Treatment Discontinuation or Death (TDT) | Time elapsed from randomization to study treatment discontinuation or death. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity. | To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to study treatment discontinuation or death (TDT). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029). |
| Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS | Radiologic scans performed at baseline then every 12 weeks for the first 156 weeks, then every 24 weeks thereafter, assessed until disease progression. Analysis of data assessed up to a maximum of 54 months. | To assess efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and potential future BRCA mutation assays (gene sequencing and large rearrangement analysis) |
| Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to First Subsequent Therapy or Death (TFST) | Assessed every 12 weeks following treatment discontinuation. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity. | To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to first subsequent therapy or death (TFST). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029). |
Countries
Australia, Brazil, Canada, China, France, Israel, Italy, Japan, Netherlands, Poland, Russia, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
Global Cohort: 391 randomised. First/Last patient randomised 03Sep2013/06Mar2015. China Cohort: 64 randomised. First/Last patient randomised 09Jan2015/22Mar2016. A total of 450 patients randomised (386 global cohort only, 64 China cohort (of which 5 included in global cohort)). Global Cohort used for hypotheses testing of study.
Pre-assignment details
It was planned that approximately 344 women in the Global Cohort, and 53 women in the China Cohort, with BRCA mutated ovarian cancer patients who are in clinical complete or partial response following first line platinum based chemotherapy were to receive olaparib 300 mg bd or matching placebo in a 2:1 ratio.
Participants by arm
| Arm | Count |
|---|---|
| Olaparib 300mg Tablets (Global Cohort & China Cohort) Taken orally twice daily | 300 |
| Placebo Tablets (Global Cohort & China Cohort) Taken orally twice daily | 150 |
| Total | 450 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study (China Cohort) | Death | 10 | 6 |
| Overall Study (China Cohort) | Withdrawal by Subject | 1 | 0 |
| Overall Study (Global Cohort) | Death | 55 | 26 |
| Overall Study (Global Cohort) | Severe non-compliance to protocol | 1 | 0 |
| Overall Study (Global Cohort) | Withdrawal by Subject | 21 | 14 |
Baseline characteristics
| Characteristic | Olaparib 300mg Tablets (Global Cohort & China Cohort) | Total | Placebo Tablets (Global Cohort & China Cohort) |
|---|---|---|---|
| Age, Continuous China Cohort | 50.7 Years STANDARD_DEVIATION 7.27 | 51.0 Years STANDARD_DEVIATION 7.44 | 51.5 Years STANDARD_DEVIATION 7.95 |
| Age, Continuous Global Cohort | 53.6 Years STANDARD_DEVIATION 9.38 | 53.5 Years STANDARD_DEVIATION 9.51 | 53.4 Years STANDARD_DEVIATION 9.79 |
| Race (NIH/OMB) China Cohort American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) China Cohort Asian | 44 Participants | 64 Participants | 20 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) China Cohort White | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Global Cohort American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Global Cohort Asian | 39 Participants | 59 Participants | 20 Participants |
| Race (NIH/OMB) Global Cohort Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Global Cohort More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Global Cohort Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Global Cohort Unknown or Not Reported | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Global Cohort White | 214 Participants | 320 Participants | 106 Participants |
| Response to previous platinum chemotherapy (as randomised) China Cohort Complete Response | 37 Participants | 55 Participants | 18 Participants |
| Response to previous platinum chemotherapy (as randomised) China Cohort Partial Response | 7 Participants | 9 Participants | 2 Participants |
| Response to previous platinum chemotherapy (as randomised) Global Cohort Complete Response | 213 Participants | 320 Participants | 107 Participants |
| Response to previous platinum chemotherapy (as randomised) Global Cohort Partial Response | 47 Participants | 71 Participants | 24 Participants |
| Sex: Female, Male China Cohort Female | 44 Participants | 64 Participants | 20 Participants |
| Sex: Female, Male China Cohort Male | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Global Cohort Female | 260 Participants | 391 Participants | 131 Participants |
| Sex: Female, Male Global Cohort Male | 0 Participants | 0 Participants | 0 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 | 55 / 260 | 27 / 131 | 10 / 44 | 6 / 20 |
| other Total, other adverse events | 253 / 260 | 117 / 130 | 43 / 44 | 18 / 20 |
| serious Total, serious adverse events | 54 / 260 | 16 / 130 | 13 / 44 | 3 / 20 |
Outcome results
Primary
Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
To determine the efficacy by progression free survival (PFS) using investigator assessment according to modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy.
Time frame: Radiologic scans performed at baseline then every 12 weeks up to 156 weeks, then every 24 weeks thereafter until objective radiological disease progression. DCO: 17 May 2018
Population: Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) \[Primary analysis\] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 300mg Tablets (Global Cohort) | Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) | NA Months |
| Placebo Tablets (Global Cohort) | Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) | 13.8 Months |
| Olaparib 300mg Tablets (China Cohort) | Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) | NA Months |
| Placebo Tablets (China Cohort) | Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) | 9.3 Months |
p-value: <0.000195% CI: [0.23, 0.41]Regression, Cox
95% CI: [0.23, 0.97]Regression, Cox
Secondary
Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O)
To compare the effects of olaparib maintenance monotherapy compared to placebo on Health-related Quality of Life (HRQoL) as assessed by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy. The TOI ranges from 0-100 and a higher score indicates a higher HRQoL.
Time frame: Questionnaires will be given to the patient at baseline, at Day 29 and then every 12 weeks for 156 weeks, then every 24 weeks or until the data cut off for the PFS analysis, change in TOI over 24 months reported
Population: Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) with a baseline and post baseline TOI scores available.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Olaparib 300mg Tablets (Global Cohort) | Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) | 0.30 Scores on a scale |
| Placebo Tablets (Global Cohort) | Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) | 3.30 Scores on a scale |
p-value: 0.00195% CI: [-4.779, -1.216]Mixed Models Analysis
Secondary
Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival
To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of overall survival (OS). Reports results of a pre-specified interim analysis; results for final OS analysis (235 OS events) anticipated 2029.
Time frame: Assessed every 4 weeks until treatment discontinues (up to a max of 156 weeks), then as per protocol. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.
Population: Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) \[Primary analysis\] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 300mg Tablets (Global Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival | NA Months |
| Placebo Tablets (Global Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival | NA Months |
| Olaparib 300mg Tablets (China Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival | NA Months |
| Placebo Tablets (China Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival | NA Months |
p-value: 0.890395% CI: [0.6, 1.53]Regression, Cox
95% CI: [0.29, 2.28]Regression, Cox
Secondary
Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression
To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to second progression (PFS2)
Time frame: Following first progression disease then assessed per local practice every 12 weeks until second progression.
Population: Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) \[Primary analysis\] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 300mg Tablets (Global Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression | NA Months |
| Placebo Tablets (Global Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression | 41.9 Months |
| Olaparib 300mg Tablets (China Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression | NA Months |
| Placebo Tablets (China Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression | NA Months |
p-value: 0.000295% CI: [0.35, 0.72]Regression, Cox
95% CI: [0.23, 1.35]Regression, Cox
Secondary
Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Study Treatment Discontinuation or Death (TDT)
To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to study treatment discontinuation or death (TDT). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).
Time frame: Time elapsed from randomization to study treatment discontinuation or death. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.
Population: Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) \[Primary analysis\] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 300mg Tablets (Global Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Study Treatment Discontinuation or Death (TDT) | 24.6 Months |
| Placebo Tablets (Global Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Study Treatment Discontinuation or Death (TDT) | 13.8 Months |
| Olaparib 300mg Tablets (China Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Study Treatment Discontinuation or Death (TDT) | 24.8 Months |
| Placebo Tablets (China Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Study Treatment Discontinuation or Death (TDT) | 8.6 Months |
p-value: <0.000195% CI: [0.51, 0.79]Regression, Cox
95% CI: [0.47, 1.42]Regression, Cox
Secondary
Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death
To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen-125 (CA-125) or death
Time frame: CA-125 performed at baseline + every 4 weeks. Radiologic scans performed at baseline + every 12 weeks up to 156 weeks, then every 24 weeks until objective radiological disease progression. DCO:17May2018
Population: Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) \[Primary analysis\] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 300mg Tablets (Global Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death | NA Months |
| Placebo Tablets (Global Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death | 12.0 Months |
| Olaparib 300mg Tablets (China Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death | NA Months |
| Placebo Tablets (China Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death | 8.9 Months |
p-value: <0.000195% CI: [0.23, 0.4]Regression, Cox
95% CI: [0.23, 0.99]Regression, Cox
Secondary
Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to First Subsequent Therapy or Death (TFST)
To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to first subsequent therapy or death (TFST). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).
Time frame: Assessed every 12 weeks following treatment discontinuation. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.
Population: Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) \[Primary analysis\] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 300mg Tablets (Global Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to First Subsequent Therapy or Death (TFST) | 51.8 Months |
| Placebo Tablets (Global Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to First Subsequent Therapy or Death (TFST) | 15.1 Months |
| Olaparib 300mg Tablets (China Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to First Subsequent Therapy or Death (TFST) | 34.3 Months |
| Placebo Tablets (China Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to First Subsequent Therapy or Death (TFST) | 10.3 Months |
p-value: <0.000195% CI: [0.22, 0.4]Regression, Cox
95% CI: [0.29, 1.23]Regression, Cox
Secondary
Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Second Subsequent Therapy or Death (TSST)
To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to second subsequent therapy or death (TSST). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).
Time frame: Assessed every 12 weeks following treatment discontinuation. Analysis performed with DCO: 17May2018. Further analyses will be performed at 7 years (descriptive), after 206 events and after 60% maturity.
Population: Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) \[Primary analysis\] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 300mg Tablets (Global Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Second Subsequent Therapy or Death (TSST) | NA Months |
| Placebo Tablets (Global Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Second Subsequent Therapy or Death (TSST) | 40.7 Months |
| Olaparib 300mg Tablets (China Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Second Subsequent Therapy or Death (TSST) | NA Months |
| Placebo Tablets (China Cohort) | Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Second Subsequent Therapy or Death (TSST) | 27.4 Months |
p-value: <0.000195% CI: [0.32, 0.63]Regression, Cox
95% CI: [0.25, 1.26]Regression, Cox
Secondary
Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS
To assess efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and potential future BRCA mutation assays (gene sequencing and large rearrangement analysis)
Time frame: Radiologic scans performed at baseline then every 12 weeks for the first 156 weeks, then every 24 weeks thereafter, assessed until disease progression. Analysis of data assessed up to a maximum of 54 months.
Population: Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) and confirmed as Myriad gBRCAm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Olaparib 300mg Tablets (Global Cohort) | Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS | NA Months |
| Placebo Tablets (Global Cohort) | Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS | 13.8 Months |
p-value: <0.000195% CI: [0.22, 0.4]Regression, Cox