In previous studies, PARP inhibitors have shown antitumor activity in ovarian cancer patients with or without a BRCA mutations, but criteria to identify BRCA wild-type patients with clinical benefit remain insufficiently investigated. In ARIEL2 Part 1, the BRCA status of 192 patients was analyzed by next-generation sequencing, and patients were divided into three predefined homologous recombination deficiency subgroups: BRCA mutant (n=40), LOH high (n=82), or LOH low (n=70). The median progression-free survival (PFS) for rucaparib treatment was 12.8 months in the BRCA mutation subgroup and 5.7 months in the LOH high subgroup, compared to 5.2 months in the LOH low subgroup. Progression-free survival was significantly longer in the BRCA mutant (hazard ratio 0·27, 95% CI 0·16–0·44, p<0·0001) and LOH high (0·62, 0·42–0·90, p=0·011) subgroups compared with the LOH low subgroup, and hazard ratios were 0.27 and 0.62, respectively. Taken together, these results suggest that using next-generation sequencing to analyze BRCA mutations and tumor LOH status in platinum-sensitive ovarian cancer can identify patients with a higher magnitude of benefit.
Swisher EM, Lin KK, Oza AM, et al., Lancet Oncol. 2017 Jan;18(1):75-87. http://www.sciencedirect.com/science/article/pii/S1470204516305599