FDA Approves Olaparib/Abiraterone Combo for BRCA+ Metastatic Castration-Resistant Prostate Cancer

FDA

The FDA has approved olaparib (Lynparza) plus abiraterone and prednisone or prednisolone for the treatment of patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer, as determined by an FDA-approved companion diagnostic test.¹

The regulatory decision is supported by findings from the phase 3 PROpel trial (NCT03732820) in which the olaparib regimen significantly improved radiographic progression-free survival (rPFS) over placebo and abiraterone alone in the intention-to-treat population (ITT) and in a subset of patients harboring BRCA mutations (n = 85). In the BRCA-mutated subset, the rPFS was not yet reached in the investigative arm vs 8 months (95% CI, 6-15) in the control arm (HR, 0.24; 95% CI, 0.12-0.45). The median overall survival (OS) was not yet reached in the olaparib arm vs 23 months (95% CI, 18-34) in the control arm (HR, 0.30; 95% CI, 0.15-0.59).

Notably, data from an exploratory analysis of 711 patients without BRCA mutations showed that the hazard ratio (HR) for rPFS was 0.77 (95% CI, 0.63-0.96) and the HR for OS was 0.92 (95% CI, 0.74-1.14), which suggests that the improvement is primary attributed to those harboring the mutation.

PROPEL

The randomized, double-blind, placebo-controlled, multicenter study enrolled patients with histologically or cytologically confirmed prostate adenocarcinoma who had at least 1 documented metastatic lesion on a bone scan or computed tomography or magnetic resonance imaging scan. Patients were required to be at least 18 years of age, and they could not have prior treatment with abiraterone. Previous docetaxel for localized or metastatic hormone-sensitive prostate cancer (mHSPC) was permitted.²

A total of 796 participants were randomly assigned 1:1 to receive olaparib at a twice-daily dose of 300 mg plus abiraterone at a daily dose of 1000 mg (n = 399) or placebo plus abiraterone (n = 397). All patients were given prednisone or prednisolone at a twice daily dose of 5 mg, as well as a gonadotropin-releasing hormone analog or prior bilateral orchiectomy. Treatment with olaparib continued until objective radiographic progression per investigator assessement or intolerable toxicity.

Stratification factors included metastases (bone only vs visceral vs other) and docetaxel treatment at mHSPC stage (yes vs no).

rPFS by RECIST v1.1 and Prostate Cancer Working Group criteria served as the trial's primary end point, and OS represented a key secondary end point.

Of the 796 patients, 11% were found to harbor a BRCA mutation. Among the 85 patients with BRCA-mutated disease, the median age was 68 years (range, 43-85) and more than half (67%) were aged 65 years or older. The majority (72%) of patients were White and had an ECOG performance status of 0 (66%). Twenty-five percent of patients previously received docetaxel. About half (53%) of patients had bone-only metastases, 15% had visceral metastases, and 32% had other metastases.

The most common toxicities experienced by 10% or more of patients who received the olaparib regimen included anemia (48%), fatigue (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%).¹ Moreover, 18% of patients required at least 1 blood transfusion and 12% needed several transfusions.

References

1. FDA approves olaparib with abiraterone and prednisone (or prednisolone) for BRCA-mutated metastatic castration-resistant prostate cancer. FDA. May 31, 2023. Accessed May 31, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-abiraterone-and-prednisone-or-prednisolone-brca-mutated-metastatic-castration
2. Olaparib (Lynparza). Prescribing information. AstraZeneca. Updated May 2023. Accessed May 31, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/208558s025lbl.pdf