Overall survival did not differ significantly between the treatment groups in the overall patient population or in patients with BRCA mutations. A previous study also showed significantly improved progression-free survival, especially in patients with BRCA mutation-related disease, but no overall survival benefit. The authors of a Comment article suggest that if the most striking progression-free survival hazard ratios reported for this class of drug in ovarian cancer are to be converted into improved overall survival, the following questions need to be addressed:
• Since BRCA mutation-associated ovarian cancer often remains platinum-sensitive during several disease recurrences, would additional benefit be recorded if PARP inhibitor maintenance were to be reinstituted at each chemotherapy-induced remission? • Can biomarkers be identified for homologous recombination DNA repair deficiency and genomic instability, which would predict benefit from PARP inhibitor treatment? • What is the potential role of PARP inhibitors in the platinum-resistant disease setting?
EU and US regulatory filings for olaparib in ovarian cancer are planned for 2017 (first-line) and 2016 (relapsed).