FDA approves Lynparza for prostate cancer subset
The FDA approved olaparib for treatment of certain men with metastatic castration-resistant prostate cancer.
The indication applies to use of olaparib (Lynparza, AstraZeneca) by men with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated disease that progressed after treatment with enzalutamide (Xtandi; Astellas Pharma, Pfizer) or abiraterone.
Olaparib — a poly(ADP-ribose) polymerase (PARP) inhibitor — has been approved for multiple uses in gynecologic, breast and pancreatic cancers.
The FDA based the new indication on results of the open-label, multicenter PROfound trial, which included 387 men with metastatic castration-resistant prostate cancer.
Researchers randomly assigned 256 men to olaparib dosed at 300 mg twice daily. The other 131 men received investigator’s choice of enzalutamide or abiraterone acetate. All men received a gonadotropin-releasing hormone analog or had prior bilateral orchiectomy.
Investigators divided the men into two cohorts based on HRR gene mutation status. Cohort A comprised those with BRCA1, BRCA2 or ATM mutations (n = 245). Cohort B comprised those with mutations in 12 other genes involved in the HRR pathway (n = 142).
Radiological PFS in cohort A served as the major efficacy outcome. Additional outcomes included confirmed objective response rate among men in cohort A with measurable disease, radiological PFS in both cohorts, and OS among men in cohort A.
Analysis of cohort A showed significant improvement among olaparib-treated men with regard to median radiological PFS (7.4 months vs 3.6 months; HR = 0.34; 95% CI, 0.25-0.47), OS (19.1 months vs. 14.7 months; HR = 0.69; 95% CI, 0.5-0.97) and ORR (33% vs 2%; P < .0001).
An analysis of both cohorts showed statistically significant improvement in median radiological PFS among men who received olaparib (5.8 months vs. 3.5 months; HR = 0.49; 95% CI, 0.38-0.63).
The most common adverse events reported among olaparib-treated men included anemia, nausea, fatigue, decreased appetite, diarrhea, vomiting, thrombocytopenia, cough and dyspnea.
A higher percentage of men treated with olaparib experienced venous thromboembolic events, including pulmonary embolism (7% vs. 3.1%).
The FDA previously granted olaparib priority review and breakthrough therapy designation for this indication.
The agency also approved two companion diagnostics — FoundationOne CDx (Foundation Medicine) and BRACAnalysis CDx (Myriad Genetic Laboratories) — to guide selection of men with metastatic castration-resistant prostate cancer who are appropriate for olaparib treatment.