FDA D.I.S.C.O. Burst Edition: FDA approval of Lynparza (olaparib), with abiraterone and prednisone, for BRCA-mutated metastatic castration-resistant prostate cancer
Regulatory approval: On May 31, 2023, the FDA approved olaparib (Lynparza) in combination with abiraterone and prednisone (or prednisolone) for adult patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic. The approval was based on PROpel, which showed a statistically significant radiographic progression-free survival benefit in the intent-to-treat population, with exploratory analyses suggesting the benefit was primarily driven by BRCA-mutated disease.
FDA approval (May 31, 2023): olaparib + abiraterone + prednisone for BRCA-mutated mCRPC
The FDA approved olaparib (Lynparza) with abiraterone and prednisone (or prednisolone) for adult patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic test.
Supporting evidence: PROpel
Efficacy was evaluated in PROpel (n=796) in mCRPC. Patients were randomized 1:1 to olaparib + abiraterone vs placebo + abiraterone, with prednisone/prednisolone. Prior systemic therapy for mCRPC was excluded; prior docetaxel for metastatic hormone-sensitive disease was allowed. Key stratification factors included site of metastases and prior docetaxel.
The major efficacy endpoint was investigator-assessed radiologic progression-free survival (rPFS) (RECIST v1.1 for soft tissue and PCWG criteria for bone); overall survival (OS) was an additional endpoint. A statistically significant rPFS improvement was reported in the intent-to-treat population.
In an exploratory subgroup of 85 BRCA-mutated patients, median rPFS was not reached with olaparib + abiraterone vs 8 months with placebo + abiraterone; OS hazard ratio was 0.30. Among 711 without BRCA mutation, rPFS HR was 0.77 and OS HR 0.92, suggesting the ITT rPFS effect was primarily attributable to BRCA-mutated patients.
Safety
Common adverse reactions (>10%) included anemia, fatigue, nausea, diarrhea, decreased appetite, lymphopenia, dizziness, and abdominal pain. 72 patients required ≥1 blood transfusion; 46 required multiple transfusions.