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EMA Committee Recommends Narrower Lynparza Indication for Metastatic Prostate Cancer Than FDA

NEW YORK – The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended approval of olaparib (AstraZeneca/Merck's Lynparza) as a treatment for metastatic castration-resistant prostate cancer (CRPC) patients with BRCA1/2 mutations who have progressed on a hormonal agent.

Following CHMP's recommendation, the European Commission will review the opinion and decide whether to approve the regimen.

To make the recommendation, the committee relied on a subgroup analysis in the PROfound trial, results of which were recently published in the New England Journal of Medicine

The study randomized patients with metastatic CRPC and homologous repair recombination (HRR) gene alterations to receive olaparib or physician's choice of either enzalutamide (Pfizer/Astellas Xtandi) or abiraterone (Janssen's Zytiga). Olaparib's activity was evaluated in two cohorts, one involving patients with mutations in BRCA1, BRCA2, or ATM, and another including patients with alterations in one of a dozen other HRR genes (BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAF51D, and RAD53L).

According to an exploratory gene-specific analysis in the NEJM paper, patients with BRCA1 and BRCA2 mutations on olaparib had at 58 percent and 41 percent lower risk of death, respectively.  However, the risk of death didn't appear to differ between treatment arms in patients with mutations in other HRR genes.

CHMP's recommendation to approve olaparib in metastatic CRPC with BRCA1/2 mutations is a more restricted indication than the one the US Food and Drug Administration granted. The FDA in May approved the drug for metastatic CRPC patients with mutations in the broader set of HRR genes evaluated in PROfound. At the European Society for Medical Oncology's Virtual Congress this weekend, oncologists discussed the gene-specific exploratory analysis within PROfound and debated the appropriateness of FDA's broader approval.