NEW YORK – AstraZeneca and Merck on Thursday announced that their PARP inhibitor olaparib (Lynparza) was approved in the EU for two new indications: as a monotherapy for previously treated patients with metastatic, castration-resistant prostate cancer harboring BRCA1/2 mutations and as a maintenance treatment in combination with bevacizumab (Genentech's Avastin) for previously treated ovarian cancer patients with homologous recombination repair deficient (HRD) tumors.
The European Commission based olaparib's mCRPC approval on the Phase III PROfound study, in which olaparib improved progression-free survival and overall survival versus the hormone agents enzalutamide (Pfizer/Astellas Xtandi) or abiraterone (Janssen's Zytiga) among patients with BRCA1/2 mutations.
Notably, when the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended this approval in September, it strayed from the US Food and Drug Administration's approval, which included mCRPC patients harboring alterations in any one of a dozen other homologous recombination repair (HRR) genes. European regulators' choice to narrow olaparib's indication to patients with BRCA1/2-mutated mCRPC was based on subgroup analysis from the PROfound study showing that while the overall population of patients with HRR alterations benefited from treatment, the benefit was not as clear in the subpopulation of patients with alterations in genes other than BRCA1/2.
As for the ovarian cancer indication, the EC's approval follows a September recommendation from CHMP based on the results of the Phase III PAOLA-1 trial, in which the combination of olaparib and bevacizumab maintenance treatment after first-line platinum-based chemotherapy reduced the risk of death or disease progression in patients with HRD-positive cancers, marked by either BRCA1/2 mutations or genomic instability. The FDA granted approval for the olaparib-bevacizumab combination for the same indication in May.