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FDA Approves Merck, AstraZeneca's Lynparza Combo for BRCA-Mutant Metastatic Prostate Cancer

NEW YORK – The US Food and Drug Administration on Wednesday approved Merck and AstraZeneca's PARP inhibitor Lynparza (olaparib) plus Janssen's Zytiga (abiraterone) and a steroid for patients with BRCA1/2-mutated metastatic castration-resistant prostate cancer.

The FDA based its approval on the results of the Phase III PROpel clinical trial, in which Lynparza plus Zytiga and a steroid — either prednisone or prednisolone — improved patients' progression-free and overall survival versus Zytiga and a steroid alone.

Although the trial enrolled all-comers, the agency based its decision to limit the approval to BRCA-mutated patients on the results of an 85-patient subgroup analysis. Patients in this subgroup harbored deleterious or suspected deleterious somatic or germline mutations in BRCA1 or BRCA2, as determined by an FDA-approved assay.

Among BRCA-mutated mCRPC patients in this subgroup who received Lynparza plus the Zytiga and steroid combination, neither the median radiographic progression-free survival nor the median overall survival had been reached at the time of the data cutoff. Among patients who received Zytiga plus the steroid and a placebo, meanwhile, the median radiographic progression-free survival was eight months and the median overall survival was 23 months.

Although the full intention-to-treat population enrolled in the PROpel trial appeared to benefit from the PARP inhibitor addition, the FDA determined that the BRCA-mutant patient population was likely driving the benefit observed in all-comers. In making this decision, the FDA weighed input from its Oncologic Drugs Advisory Committee, which voted 11 to 1 in April for Lynparza's approval in the biomarker-defined subset.

"There is a critical unmet need for new first-line treatment options for patients with BRCA-mutated metastatic mCRPC," Dave Fredrickson, the executive VP of AstraZeneca's oncology business unit, said in a statement. "This approval underscores the importance of BRCA testing at metastatic diagnosis."