Phase 3
N=266
Olaparib Treatment in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA) Mutated Ovarian Cancer Patients Who Have Progressed at Least 6 Months After Last Platinum Treatment and Have Received at Least 2 Prior Platinum Treatments
Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity
Bottom Line
View on ClinicalTrials.gov: NCT02282020 ↗Enrolled (actual)
266
Serious AEs
23.6%
Results posted
Dec 2019
Primary outcome: Primary: Objective Response Rate (ORR) — 109; 37 Count of Participants — p=0.002
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- OLAPARIB (Drug); Single agent chemotherapy (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- AstraZeneca
- Primary completion
- Oct 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Objective Response Rate (ORR) |
109; 37 | 0.002 sig |
| SECONDARY Progression Free Survival (PFS) |
13.4; 9.2 | 0.013 sig |
| SECONDARY Time From Randomisation to Second Progression (PFS2) |
23.6; 19.6 | 0.229 |
| SECONDARY Overall Survival (OS) |
34.9; 32.9 | 0.714 |
| SECONDARY Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death |
11.1; 7.9 | 0.005 sig |
| SECONDARY Time From Randomization To First Subsequent Therapy Or Death (TFST) |
15.4; 10.9 | <0.001 sig |
| SECONDARY Time From Randomization To Second Subsequent Therapy Or Death (TSST) |
25.2; 19.9 | 0.089 |
| SECONDARY Time From Randomization To Study Treatment Discontinuation Or Death (TDT) |
13.1; 5.1 | <0.001 sig |
| SECONDARY Duration of Response (DoR) |
9.4; 10.2 | — |
| SECONDARY Time to Response (TTR) |
2.0; 3.5 | — |
| SECONDARY Mean Change From Baseline In Trial Outcome Index (TOI) Score |
-2.4; -3.6 | 0.108 |
| SECONDARY Number of Participants Who Show an Improvement in TOI Score |
25; 5 | 0.092 |
| SECONDARY Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR) |
103; 36 | 0.004 sig |
| SECONDARY Number of Participants Who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR) |
105; 48 | 0.014 sig |
| SECONDARY Number of Participants Who Experienced Second Progression or Death (PFS2) in BRCA Gene Population |
110; 48 | 0.213 |
| SECONDARY Overall Survival (OS) in BRCA Gene Population |
111; 45 | 0.699 |
| SECONDARY Number of Participants Who Discontinued Study Treatment or Died in BRCA Gene Population |
151; 76 | <0.001 sig |
| SECONDARY Number of Participants Who Received Subsequent Chemotherapy or Died in BRCA Gene Population |
138; 66 | <0.001 sig |
| SECONDARY Number of Participants Who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population |
127; 56 | 0.055 |
| SECONDARY Geometric Mean Plasma Concentration of Olaparib |
4.76; 1.78 | — |
| SECONDARY Number of Participants Who Experience at Least One Adverse Event (AE) |
175; 73 | — |
Summary
Comparison of olaparib vs. physician's choice of single agent standard of care non-platinum based chemotherapy in patients with germline Breast Cancer susceptibility gene (gBRCA) mutated ovarian cancer who have progressed at least 6 months after the last platinum based chemotherapy. Patient should have received at least 2 prior lines of platinum based chemotherapy. The aim of the study is to assess the efficacy and safety of olaparib tablets.
Eligibility Criteria
Inclusion Criteria
- Patients must be ≥ 18 years of age
- Patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and/or fallopian tube cancer) or high grade endometrioid cancer. Patients are eligible to undergo BRCA testing even if they have not yet had recurrence or progression of disease >6 months (>/=183 days) after completion of their last platinum therapy.
- Documented germline mutation in Breast Cancer susceptibility genes: BRCA1 and/or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)
- At least one lesion that can be accurately assessed at baseline by CT/MRI and is suitable for repeated assessment.
- Patients must have received at least 2 prior platinum based lines of chemotherapy - Patients must be partially platinum sensitive or platinum sensitive
- Patients must be suitable to start treatment with single agent chemotherapy based on physician's choice
- Patients must have normal organ and bone marrow function measured within 28 days of randomisation,
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Patients must have a life expectancy ≥ 16 weeks
- Formalin fixed, paraffin embedded tumour sample from the primary or recurrent cancer must be available for central testing.
Exclusion Criteria
- BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental
- Exposure to any investigational product within 30 days or 5 half lives (whichever is longer) prior to randomisation
- Any previous treatment with a Polyadenosine 5'diphosphoribose polymerisation (PARP) inhibitor, including olaparib.
- Patients who have platinum resistant or refractory disease
- Patients receiving any systemic chemotherapy within 3 weeks prior to first dose of study treatment
- Previous single agent exposure to the selected chemotherapy regimen for randomisation. - Prior malignancy in the last 5 years, unless curatively treated and recurrence free (few exceptions apply).
Data sourced from ClinicalTrials.gov (NCT02282020). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.