FDA approves olaparib with abiraterone and prednisone (or prednisolone) 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. Approval was supported by the PROpel trial, including an exploratory BRCA-mutated subgroup analysis showing improved rPFS versus placebo plus abiraterone.
FDA approval (May 31, 2023)
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 (NCT03732820)
Efficacy was evaluated in PROpel, which enrolled 796 patients with mCRPC randomized 1:1 to olaparib + abiraterone vs placebo + abiraterone, with prednisone/prednisolone. Patients with prior systemic therapy for mCRPC were excluded; prior docetaxel for metastatic hormone-sensitive disease was allowed. BRCA status was retrospectively assessed using FoundationOne CDx and FoundationOne Liquid CDx.
The primary endpoint was investigator-assessed radiological PFS (rPFS); overall survival (OS) was also assessed. A statistically significant rPFS improvement was observed in the ITT population. In an exploratory subgroup of 85 patients (11%) with BRCAm, median rPFS was not reached with olaparib + abiraterone vs 8 months with placebo + abiraterone (HR 0.24, 95% CI 0.12–0.45); OS HR was 0.30 (95% CI 0.15–0.59). In 711 patients without BRCAm, rPFS HR was 0.77 (95% CI 0.63–0.96) and OS HR 0.92 (95% CI 0.74–1.14), suggesting ITT rPFS benefit was primarily attributable to BRCAm.
Safety and dosing highlights
Common adverse reactions (≥10%) with olaparib + abiraterone included anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%). 18% required ≥1 transfusion.
Recommended dosing: olaparib 300 mg PO BID; abiraterone 1000 mg PO daily with prednisone/prednisolone 5 mg PO BID; plus concurrent GnRH analog unless prior bilateral orchiectomy.