BRCA or HRR+ Mutated Ovarian Cancer Patients
Conditions
Brief summary
This is a prospective, open-label, single arm, multi-center study to assess the real world clinical effectiveness and safety of olaparib maintenance monotherapy as the capsule formulation (in line with the EU approved prescribing information) and will be conducted in platinum-sensitive relapsed high grade epithelial ovarian cancer patients (including patients with primary peritoneal and / or fallopian tube cancer) who carry germline or somatic BRCA mutations (documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious \[known or predicted to be detrimental/lead to loss of function\]).
Detailed description
The study will recruit approximately 250 patients with sBRCAm disease or gBRCAm disease, with the aim to accrue a minimum of 50 patients with sBRCAm disease. Patients with an unknown germline BRCA mutated status or gBRCAwt disease or previously identified as having a BRCAm disease by a tumour test will be considered for screening and will undergo, upon informed consent signature, central tumor and blood testing to determine their BRCA mutation status. In addition to central BRCA testing, patients screened for the study with unknown BRCA status or with known gBRCAwt status, for whom an adequate archival tumour tissue sample is available, will be tested for qualifying HRR gene alterations. Patients confirmed to carry a deleterious or suspected deleterious BRCA-independent genetic alteration in any of 13 genes involved in the Homologous Recombination Repair (HRR) pathway (HRRm cohort) will be allowed into an additional exploratory cohort (HRRm cohort). It is expected that approximately 25 patients will be included in the HRRm cohort before the target number of 250 patients with BRCAm disease is reached. Patients will be assigned olaparib capsules orally 400 mg twice daily. They should initiate olaparib treatment within 8 weeks after their last dose of platinum-containing chemotherapy (last dose is the day of the last infusion) and will be assessed every 4 weeks whilst on treatment. All patients will have clinical and objective radiological tumour assessments according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines at baseline and every 12 weeks relative to date of enrolment, until objective radiological disease progression as determined by the investigator. Patients could continue to receive olaparib for as long as determined by the investigator, until objective radiological disease progression or as long as in the investigator's opinion they are benefiting from treatment in relation to other clinical assessments and they do not meet any other discontinuation criteria. Once a patient has discontinued olaparib she will be managed as per local clinical practice but will remain in the study and data will be collected on subsequent treatments, progression, overall survival and safety. For exploratory analysis purposes, patients will be asked to provide consent to: 1. Optional tumour samples at baseline and at disease progression 2. An optional blood sample only for patients with a confirmed sBRCAm or HRRm disease
Interventions
DRUGOlaparib
Olaparib Capsule - 50 mg. Olaparib capsules will be packed in high-density polyethylene (HDPE) bottles with child-resistant closures. Each bottle will contain 120 capsules and 4 bottles will be dispensed for a 4 weekly visit, with a 2 day overage. Patients will be administered olaparib capsules orally at a dose of 400 mg twice daily. Eight 50 mg olaparib capsules should be taken at the same time each day approximately 12 hours apart with approximately 240 mL of water.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of informed consent prior to any study specific procedures 2. Age 18 years or over 3. Documented germline or somatic mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function) \[Genetic counselling for patients with germline BRCA mutations should be performed according to local regulations\] Or Tumour BRCAwt status and documented qualifying mutation in any of 13 genes involved in the HRR pathway, excluding BRCA1 and BRCA2 (ATM, BARD1, BRIP1,CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D,and RAD54L), identified by the Lynparza HRR Assay in archival tumour tissue (i.e.,BRCA-independent HRRm) 4. Patients with platinum sensitive relapsed high grade epithelial ovarian cancers (including primary peritoneal and/or fallopian tube cancer): \- Platinum sensitive disease is defined as disease progression ≥6 months after completion of their last dose of platinum based chemotherapy 5. Patients should have received at least 2 previous lines of platinum containing therapy prior to enrolment: \- For the last chemotherapy course immediately prior to enrolment on the study, patients must be, in the opinion of the investigator, in response (partial or complete radiological response) and no evidence of a rising CA-125, following completion of this chemotherapy course. 6. Patients must have normal organ and bone marrow function measured within 28 days of enrolment, as defined below: * Haemoglobin ≥ 10.0 g/dL with no blood transfusions in the past 28 days * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L * Platelet count ≥ 100 x 109/L 7. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase \[SGOT\]) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase \[SGPT\]) ≤ 2.5 x institutional ULN unless liver metastases are present in which case they must be ≤ 5x ULN 8. Creatinine clearance \> 50 ml/min (calculated) 9. Patients must be postmenopausal or have evidence of non-childbearing status for women of childbearing potential. Postmenopausal is defined as any of the following: * Amenorrhoea for 1 year or more following cessation of exogenous hormonal treatments * For women under 50 years old, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range * Radiation-induced oophorectomy, with interval of 1 year or more since last menses * Chemotherapy-induced menopause, with interval of 1 year or more since last menses * Surgical sterilisation (bilateral oophorectomy or hysterectomy).
Exclusion criteria
1. Patients previously diagnosed with gBRCAm disease 2. Participation in another clinical study with an investigational product during the most recent chemotherapy course 3. Patients with a known hypersensitivity to olaparib or any of the excipients of the product 4. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) or major surgery within 3 weeks prior to olaparib treatment. Major surgery within 3 weeks of starting study treatment and patients must have recovered from any effects of any major surgery 5. Persistent toxicities Common Terminology Criteria for Adverse Event (CTCAE) grade 2 caused by previous cancer therapy, excluding alopecia 6. Patients with myelodysplastic syndrome/acute myeloid leukaemia 7. Immuno-compromised patients e.g., Human Immunodeficiency Virus (HIV) requiring treatment or active Hepatitis B or C 8. Patients with symptomatic uncontrolled brain metastases. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease (SD) for 28 days 9. Patients considered to be at a high medical risk due to a serious, uncontrolled medical disorder, systemic disease or active, uncontrolled infection 10. Currently pregnant (confirmed with a positive pregnancy test) or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Tumour assessments at baseline then every 12 weeks relative to date of enrolment until RECIST 1.1-defined progression. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months). | To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of PFS. The PFS was defined as the time from the date of enrolment until date of objective radiological disease progression (assessed by the Investigator via Response Evaluation Criteria in Solid Tumors, version 1.1 \[RECIST 1.1\]), or death (by any cause in absence of disease progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to disease progression. Objective progression was defined as at least a 20% increase in the sum of the diameters of the target lesions (compared to previous minimum sum) and an absolute increase of \> 5 millimeters, or an overall non-target lesion assessment of progression or a new lesion. The data cut-off (DCO) for the primary analysis of the study occurred after approximately 60% maturity of PFS in the sBRCAm and all BRCAm patient populations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Second Progression (PFS2) or Death; Assessed at Primary Analysis | Tumour assessments (and blood samples for CA-125, if applicable) at baseline then every 12 weeks relative to date of enrolment until second progression. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months). | To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of PFS2. The PFS2 was defined as the time from the date of enrolment to the earliest progression event subsequent to that used for the primary variable PFS or death (by any cause) in the absence of progression. Patients whose progression event for PFS was death had this counted as a progression event for PFS2 also. The date of second progression was recorded by the Investigator and defined according to local standard clinical practice and could involve any of the following: objective radiological, symptomatic, cancer antigen-125 (CA-125) progression or death. Pre-specified analysis of PFS2 was performed at the time of the primary analysis; a further analysis of PFS2 was performed at the final analysis (and reported as a separate outcome measure). |
| Time to First Subsequent Therapy (Treatment) or Death (TFST); Assessed at Primary Analysis | From enrolment to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months). | To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TFST. The TFST was defined as the time from the date of enrolment to the earlier of first subsequent anti-cancer therapy start date (excluding radiotherapy), or death date. Pre-specified analysis of TFST was performed at the time of the primary analysis; a further analysis of TFST was performed at the final analysis (and reported as a separate outcome measure). |
| Time to Second Subsequent Therapy (Treatment) or Death (TSST); Assessed at Primary Analysis | From enrolment to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months). | To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TSST. The TSST was defined as the time from the date of enrolment to the earlier of the date of second subsequent anti-cancer therapy start date, or death date. Pre-specified analysis of TSST was performed at the time of the primary analysis; a further analysis of TSST was performed at the final analysis (and reported as a separate outcome measure). |
| Time to Discontinuation of Treatment or Death (TDT) | From enrolment to study treatment discontinuation or death (up to maximum of 6 years). | To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TDT. The TDT was defined as the time from the date of enrolment to the earlier of the date of study treatment discontinuation or death. |
| Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | QoL questionnaires at baseline, Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. QoL questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose. | To assess the Quality of Life (QoL) of patients with BRCAm and sBRCAm ovarian cancer by evaluation of FACT-O TOI. The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire version 4. The FACT-O TOI score ranges from 0-100, with a higher score indicating better QoL. A change (increase or decrease) in score of at least 10 points from baseline was defined as clinically meaningful. A positive change in score from baseline indicates an improvement. |
| Overall Survival (OS); Assessed at Primary Analysis | From baseline until death due to any cause. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months). | To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of OS. The OS was defined as the time from the date of enrolment until death due to any cause regardless of whether the patient withdrew from therapy or received another anti-cancer therapy. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Pre-specified analysis of OS was performed at the time of primary analysis of PFS; a further analysis of OS was performed after approximately 60% maturity of OS in the sBRCAm and all BRCAm patient populations (and reported as a separate outcome measure). |
| Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | FLIE questionnaires at baseline, weekly until Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. FLIE questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose. | The FLIE captures the impact of nausea and vomiting on patient's QoL. The FLIE consists of 18 items (9 nausea-specific and 9 vomiting-specific items), rated from 1 to 7. Two domain scores and a total score are derived; the total score ranges 18-126 and a higher score indicates a lower impact (and better QoL). A positive change in score from baseline indicates an improvement. |
| OS; Assessed at Final Analysis | From baseline until death due to any cause (up to maximum of 6 years). | To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of OS. The OS was defined as the time from the date of enrolment until death due to any cause regardless of whether the patient withdrew from therapy or received another anti-cancer therapy. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. |
| PFS2 or Death; Assessed at Final Analysis | Tumour assessments (and blood samples for CA-125, if applicable) at baseline then every 12 weeks relative to date of enrolment until second progression (up to maximum of 6 years). | To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of PFS2. The PFS2 was defined as the time from the date of enrolment to the earliest progression event subsequent to that used for the primary variable PFS or death (by any cause) in the absence of progression. Patients whose progression event for PFS was death had this counted as a progression event for PFS2 also. The date of second progression was recorded by the Investigator and defined according to local standard clinical practice and could involve any of the following: objective radiological, symptomatic, CA-125 progression or death. |
| TFST; Assessed at Final Analysis | From enrolment to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation (up to maximum of 6 years). | To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TFST. The TFST was defined as the time from the date of enrolment to the earlier of first subsequent anti-cancer therapy start date (excluding radiotherapy), or death date. |
| TSST; Assessed at Final Analysis | From enrolment to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation (up to maximum of 6 years). | To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TSST. The TSST was defined as the time from the date of enrolment to the earlier of the date of second subsequent anti-cancer therapy start date, or death date. |
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | QoL questionnaires at baseline, Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. QoL questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose. | To assess the QoL of patients with BRCAm and sBRCAm ovarian cancer by evaluation of FACIT-F. The FACIT-F is a 13-item questionnaire to assess patients' fatigue experience and its impact on their daily lives over the past 7 days. The FACIT-F total score ranges from 0-52, with a higher score indicating a lower level of fatigue (and better QoL). Changes in scores of ≥3 points were defined to be clinically meaningful. A positive change in score from baseline indicates an improvement. |
Countries
Bulgaria, Canada, Czechia, Hungary, Italy, Poland, Spain, United Kingdom
Participant flow
Recruitment details
This study was conducted in 8 countries in patients with platinum sensitive relapsed high grade epithelial ovarian (including fallopian tube or primary peritoneal) cancer, who were in complete or partial response to platinum-based chemotherapy.
Pre-assignment details
181 patients enrolled and assigned to olaparib: 145 with breast cancer susceptibility gene mutation (BRCAm) status (87 with germline mutations \[gBRCAm\], 55 with somatic mutations \[sBRCAm\] and 3 with undetermined BRCAm status), 33 with BRCA-independent homologous recombination repair mutation (HRRm\^) status, and 3 enrolled in error (unassigned).
Participants by arm
| Arm | Count |
|---|---|
| Overall BRCAm Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort had BRCAm status, comprising of those with sBRCAm or gBRCAm disease, as well as any patients where the germline or somatic BRCA mutation status was not determined. | 145 |
| HRRm^ Patients received olaparib capsules orally 400 mg twice daily. Patients in this exploratory cohort had a qualifying mutation in any of the 13 genes involved in the HRR pathway (excluding BRCA1 and BRCA2) (i.e. BRCA-independent HRRm\^). | 33 |
| Unassigned (Not BRCAm, Not HRRm^) Patients received olaparib capsules orally 400 mg twice daily. Patients in this cohort were not classified as being a part of either the BRCAm group or the HRRm\^ group and were enrolled in error. | 3 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 48 | 8 | 1 |
| Overall Study | Eligibility criteria not fulfilled | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 10 | 0 | 1 |
| Overall Study | Other | 0 | 2 | 0 |
| Overall Study | Patient decision | 37 | 8 | 0 |
Baseline characteristics
| Characteristic | Overall BRCAm | HRRm^ | Unassigned (Not BRCAm, Not HRRm^) | Total |
|---|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 10.75 | 62.2 years STANDARD_DEVIATION 9.74 | 58.7 years STANDARD_DEVIATION 9.07 | 60.5 years STANDARD_DEVIATION 10.52 |
| Age, Customized ≥35 to <50 years | 27 Participants | 3 Participants | 0 Participants | 30 Participants |
| Age, Customized <35 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized ≥50 to <65 years | 54 Participants | 13 Participants | 2 Participants | 69 Participants |
| Age, Customized ≥65 to <80 years | 48 Participants | 15 Participants | 1 Participants | 64 Participants |
| Age, Customized ≥80 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 142 Participants | 31 Participants | 3 Participants | 176 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 142 Participants | 31 Participants | 3 Participants | 176 Participants |
| Sex: Female, Male Female | 145 Participants | 33 Participants | 3 Participants | 181 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 | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 40 / 87 | 28 / 55 | 68 / 145 | 14 / 33 | 2 / 3 |
| other Total, other adverse events | 79 / 87 | 51 / 55 | 131 / 143 | 29 / 32 | 1 / 2 |
| serious Total, serious adverse events | 27 / 87 | 13 / 55 | 40 / 143 | 7 / 32 | 1 / 2 |
Outcome results
Primary
Progression-Free Survival (PFS)
To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of PFS. The PFS was defined as the time from the date of enrolment until date of objective radiological disease progression (assessed by the Investigator via Response Evaluation Criteria in Solid Tumors, version 1.1 \[RECIST 1.1\]), or death (by any cause in absence of disease progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to disease progression. Objective progression was defined as at least a 20% increase in the sum of the diameters of the target lesions (compared to previous minimum sum) and an absolute increase of \> 5 millimeters, or an overall non-target lesion assessment of progression or a new lesion. The data cut-off (DCO) for the primary analysis of the study occurred after approximately 60% maturity of PFS in the sBRCAm and all BRCAm patient populations.
Time frame: Tumour assessments at baseline then every 12 weeks relative to date of enrolment until RECIST 1.1-defined progression. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).
Population: The FAS included all enrolled patients who were assigned olaparib. The primary endpoint results for PFS assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall BRCAm | Progression-Free Survival (PFS) | 18.0 months |
| sBRCAm | Progression-Free Survival (PFS) | 16.6 months |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time
To assess the Quality of Life (QoL) of patients with BRCAm and sBRCAm ovarian cancer by evaluation of FACT-O TOI. The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire version 4. The FACT-O TOI score ranges from 0-100, with a higher score indicating better QoL. A change (increase or decrease) in score of at least 10 points from baseline was defined as clinically meaningful. A positive change in score from baseline indicates an improvement.
Time frame: QoL questionnaires at baseline, Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. QoL questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose.
Population: The FAS-FACT-O-TOI population included all enrolled patients who were assigned olaparib excluding patients who did not have FACT-O TOI score at baseline and patients who did not have any FACT-O TOI score post-baseline. The secondary endpoint results for FACT-O TOI assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall BRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 64 | 1.8 scores on a scale | Standard Deviation 9.88 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 16 | -1.3 scores on a scale | Standard Deviation 10.04 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 76 | 1.4 scores on a scale | Standard Deviation 9.27 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 40 | 1.6 scores on a scale | Standard Deviation 10.72 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 88 | 2.0 scores on a scale | Standard Deviation 9.97 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 4 | -2.2 scores on a scale | Standard Deviation 9.82 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 100 | -0.2 scores on a scale | Standard Deviation 9.41 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Discontinuation of olaparib visit | -4.7 scores on a scale | Standard Deviation 13 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 52 | 3.2 scores on a scale | Standard Deviation 9.03 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | 30 days post discontinuation | -8.0 scores on a scale | Standard Deviation 13.45 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 28 | 1.2 scores on a scale | Standard Deviation 9.44 |
| sBRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | 30 days post discontinuation | -4.3 scores on a scale | Standard Deviation 13.36 |
| sBRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 4 | -1.9 scores on a scale | Standard Deviation 9.59 |
| sBRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 16 | -0.3 scores on a scale | Standard Deviation 10.85 |
| sBRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 28 | 3.2 scores on a scale | Standard Deviation 10.25 |
| sBRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 40 | 4.1 scores on a scale | Standard Deviation 10.48 |
| sBRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 52 | 4.9 scores on a scale | Standard Deviation 7.84 |
| sBRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 64 | 0.8 scores on a scale | Standard Deviation 9.72 |
| sBRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 76 | 0.3 scores on a scale | Standard Deviation 9.83 |
| sBRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 88 | 1.5 scores on a scale | Standard Deviation 10.86 |
| sBRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Discontinuation of olaparib visit | -7.4 scores on a scale | Standard Deviation 15.53 |
| sBRCAm | Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time | Week 100 | -3.5 scores on a scale | Standard Deviation 7.54 |
Secondary
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time
To assess the QoL of patients with BRCAm and sBRCAm ovarian cancer by evaluation of FACIT-F. The FACIT-F is a 13-item questionnaire to assess patients' fatigue experience and its impact on their daily lives over the past 7 days. The FACIT-F total score ranges from 0-52, with a higher score indicating a lower level of fatigue (and better QoL). Changes in scores of ≥3 points were defined to be clinically meaningful. A positive change in score from baseline indicates an improvement.
Time frame: QoL questionnaires at baseline, Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. QoL questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose.
Population: The FAS-FACIT-F population included all enrolled patients who were assigned olaparib excluding patients who did not have FACIT-F total score at baseline and patients who did not have any FACIT-F total score post-baseline. The secondary endpoint results for FACIT-F assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall BRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 100 | -0.4 scores on a scale | Standard Deviation 8.59 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 4 | -2.9 scores on a scale | Standard Deviation 8.21 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 16 | -2.5 scores on a scale | Standard Deviation 7.54 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 28 | -1.2 scores on a scale | Standard Deviation 7.95 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 40 | -0.3 scores on a scale | Standard Deviation 7.91 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 52 | 0.6 scores on a scale | Standard Deviation 7.43 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 64 | 0.8 scores on a scale | Standard Deviation 7.26 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 76 | -0.3 scores on a scale | Standard Deviation 8.57 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 88 | 0.3 scores on a scale | Standard Deviation 8.45 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Discontinuation of olaparib visit | -2.3 scores on a scale | Standard Deviation 9.01 |
| Overall BRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | 30 days post discontinuation | -5.2 scores on a scale | Standard Deviation 11.16 |
| sBRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 100 | -1.3 scores on a scale | Standard Deviation 8.75 |
| sBRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 64 | 0.5 scores on a scale | Standard Deviation 8.47 |
| sBRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 4 | -2.9 scores on a scale | Standard Deviation 7.58 |
| sBRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | 30 days post discontinuation | -3.8 scores on a scale | Standard Deviation 9.65 |
| sBRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 16 | -2.7 scores on a scale | Standard Deviation 9.26 |
| sBRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 76 | -1.1 scores on a scale | Standard Deviation 8.74 |
| sBRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 28 | -0.6 scores on a scale | Standard Deviation 7.25 |
| sBRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Discontinuation of olaparib visit | -2.7 scores on a scale | Standard Deviation 9.32 |
| sBRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 40 | 0.9 scores on a scale | Standard Deviation 7.02 |
| sBRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 88 | -0.9 scores on a scale | Standard Deviation 5.81 |
| sBRCAm | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time | Week 52 | 1.3 scores on a scale | Standard Deviation 7.25 |
Secondary
Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time
The FLIE captures the impact of nausea and vomiting on patient's QoL. The FLIE consists of 18 items (9 nausea-specific and 9 vomiting-specific items), rated from 1 to 7. Two domain scores and a total score are derived; the total score ranges 18-126 and a higher score indicates a lower impact (and better QoL). A positive change in score from baseline indicates an improvement.
Time frame: FLIE questionnaires at baseline, weekly until Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. FLIE questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose.
Population: The FAS-FLIE population included all enrolled patients who were assigned olaparib excluding patients who did not have FLIE total score at baseline and patients who did not have any FLIE total score post-baseline. The secondary endpoint results for FLIE assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 1 | -6.1 scores on a scale | Standard Deviation 18.62 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 2 | -4.5 scores on a scale | Standard Deviation 18.4 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 3 | -4.1 scores on a scale | Standard Deviation 14.57 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 4 | -4.8 scores on a scale | Standard Deviation 18.48 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 16 | -2.3 scores on a scale | Standard Deviation 11.5 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 28 | -1.6 scores on a scale | Standard Deviation 13.87 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 40 | -0.1 scores on a scale | Standard Deviation 14.07 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 52 | 0.9 scores on a scale | Standard Deviation 14.41 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 64 | -0.2 scores on a scale | Standard Deviation 15.93 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 76 | 0.9 scores on a scale | Standard Deviation 14.14 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 88 | 2.2 scores on a scale | Standard Deviation 10.04 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 100 | 0.4 scores on a scale | Standard Deviation 10.37 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Discontinuation of olaparib visit | -0.7 scores on a scale | Standard Deviation 20.17 |
| Overall BRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | 30 days post discontinuation | -5.2 scores on a scale | Standard Deviation 17.02 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 88 | -1.3 scores on a scale | Standard Deviation 9.29 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 1 | -1.6 scores on a scale | Standard Deviation 18.28 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 52 | -1.9 scores on a scale | Standard Deviation 11.64 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 2 | -2.6 scores on a scale | Standard Deviation 15.97 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Discontinuation of olaparib visit | -8.8 scores on a scale | Standard Deviation 21.57 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 3 | -3.9 scores on a scale | Standard Deviation 13.23 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 64 | -1.0 scores on a scale | Standard Deviation 20.77 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 4 | -5.4 scores on a scale | Standard Deviation 19.92 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 100 | 0.1 scores on a scale | Standard Deviation 13.19 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 16 | -6.3 scores on a scale | Standard Deviation 11 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 76 | 0.6 scores on a scale | Standard Deviation 6.6 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 28 | -3.0 scores on a scale | Standard Deviation 7.94 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | 30 days post discontinuation | -5.6 scores on a scale | Standard Deviation 15.69 |
| sBRCAm | Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time | Week 40 | -3.2 scores on a scale | Standard Deviation 14.56 |
Secondary
OS; Assessed at Final Analysis
To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of OS. The OS was defined as the time from the date of enrolment until death due to any cause regardless of whether the patient withdrew from therapy or received another anti-cancer therapy. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive.
Time frame: From baseline until death due to any cause (up to maximum of 6 years).
Population: The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for OS assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall BRCAm | OS; Assessed at Final Analysis | 46.8 months |
| sBRCAm | OS; Assessed at Final Analysis | 43.2 months |
Secondary
Overall Survival (OS); Assessed at Primary Analysis
To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of OS. The OS was defined as the time from the date of enrolment until death due to any cause regardless of whether the patient withdrew from therapy or received another anti-cancer therapy. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Pre-specified analysis of OS was performed at the time of primary analysis of PFS; a further analysis of OS was performed after approximately 60% maturity of OS in the sBRCAm and all BRCAm patient populations (and reported as a separate outcome measure).
Time frame: From baseline until death due to any cause. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).
Population: The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for OS assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall BRCAm | Overall Survival (OS); Assessed at Primary Analysis | 47.6 months |
| sBRCAm | Overall Survival (OS); Assessed at Primary Analysis | NA months |
Secondary
PFS2 or Death; Assessed at Final Analysis
To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of PFS2. The PFS2 was defined as the time from the date of enrolment to the earliest progression event subsequent to that used for the primary variable PFS or death (by any cause) in the absence of progression. Patients whose progression event for PFS was death had this counted as a progression event for PFS2 also. The date of second progression was recorded by the Investigator and defined according to local standard clinical practice and could involve any of the following: objective radiological, symptomatic, CA-125 progression or death.
Time frame: Tumour assessments (and blood samples for CA-125, if applicable) at baseline then every 12 weeks relative to date of enrolment until second progression (up to maximum of 6 years).
Population: The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for PFS2 assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall BRCAm | PFS2 or Death; Assessed at Final Analysis | 34.0 months |
| sBRCAm | PFS2 or Death; Assessed at Final Analysis | 29.3 months |
Secondary
TFST; Assessed at Final Analysis
To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TFST. The TFST was defined as the time from the date of enrolment to the earlier of first subsequent anti-cancer therapy start date (excluding radiotherapy), or death date.
Time frame: From enrolment to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation (up to maximum of 6 years).
Population: The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TFST assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall BRCAm | TFST; Assessed at Final Analysis | 32.1 months |
| sBRCAm | TFST; Assessed at Final Analysis | 31.7 months |
Secondary
Time to Discontinuation of Treatment or Death (TDT)
To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TDT. The TDT was defined as the time from the date of enrolment to the earlier of the date of study treatment discontinuation or death.
Time frame: From enrolment to study treatment discontinuation or death (up to maximum of 6 years).
Population: The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TDT assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall BRCAm | Time to Discontinuation of Treatment or Death (TDT) | 19.8 months |
| sBRCAm | Time to Discontinuation of Treatment or Death (TDT) | 19.0 months |
Secondary
Time to First Subsequent Therapy (Treatment) or Death (TFST); Assessed at Primary Analysis
To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TFST. The TFST was defined as the time from the date of enrolment to the earlier of first subsequent anti-cancer therapy start date (excluding radiotherapy), or death date. Pre-specified analysis of TFST was performed at the time of the primary analysis; a further analysis of TFST was performed at the final analysis (and reported as a separate outcome measure).
Time frame: From enrolment to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).
Population: The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TFST assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall BRCAm | Time to First Subsequent Therapy (Treatment) or Death (TFST); Assessed at Primary Analysis | 37.6 months |
| sBRCAm | Time to First Subsequent Therapy (Treatment) or Death (TFST); Assessed at Primary Analysis | 31.5 months |
Secondary
Time to Second Progression (PFS2) or Death; Assessed at Primary Analysis
To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of PFS2. The PFS2 was defined as the time from the date of enrolment to the earliest progression event subsequent to that used for the primary variable PFS or death (by any cause) in the absence of progression. Patients whose progression event for PFS was death had this counted as a progression event for PFS2 also. The date of second progression was recorded by the Investigator and defined according to local standard clinical practice and could involve any of the following: objective radiological, symptomatic, cancer antigen-125 (CA-125) progression or death. Pre-specified analysis of PFS2 was performed at the time of the primary analysis; a further analysis of PFS2 was performed at the final analysis (and reported as a separate outcome measure).
Time frame: Tumour assessments (and blood samples for CA-125, if applicable) at baseline then every 12 weeks relative to date of enrolment until second progression. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).
Population: The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for PFS2 assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall BRCAm | Time to Second Progression (PFS2) or Death; Assessed at Primary Analysis | 30.9 months |
| sBRCAm | Time to Second Progression (PFS2) or Death; Assessed at Primary Analysis | 24.7 months |
Secondary
Time to Second Subsequent Therapy (Treatment) or Death (TSST); Assessed at Primary Analysis
To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TSST. The TSST was defined as the time from the date of enrolment to the earlier of the date of second subsequent anti-cancer therapy start date, or death date. Pre-specified analysis of TSST was performed at the time of the primary analysis; a further analysis of TSST was performed at the final analysis (and reported as a separate outcome measure).
Time frame: From enrolment to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).
Population: The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TSST assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall BRCAm | Time to Second Subsequent Therapy (Treatment) or Death (TSST); Assessed at Primary Analysis | 47.6 months |
| sBRCAm | Time to Second Subsequent Therapy (Treatment) or Death (TSST); Assessed at Primary Analysis | NA months |
Secondary
TSST; Assessed at Final Analysis
To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of TSST. The TSST was defined as the time from the date of enrolment to the earlier of the date of second subsequent anti-cancer therapy start date, or death date.
Time frame: From enrolment to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation (up to maximum of 6 years).
Population: The FAS included all enrolled patients who were assigned olaparib. The secondary endpoint results for TSST assessment included only BRCAm and sBRCAm patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Overall BRCAm | TSST; Assessed at Final Analysis | 38.4 months |
| sBRCAm | TSST; Assessed at Final Analysis | 32.1 months |