Under the sea.

Treating recurrent ovarian cancer can make you feel like a fish out of water. Luckily we now have initial results of the ARIEL3 trial that randomized patients 2:1 to the PARP inhibitor rucaparib versus placebo following >6 months of ovarian cancer control after >1 standard platinum-based chemo regimen. The stratification is where things get interesting. Outcomes were measured on three nested cohorts: the most inclusive was [1] the intention to treat cohort (n=564), which was whittled down to [2] the homologous recombination deficient cohort (n=354) with any BRCA anomaly including loss-of-heterozygosity, which was further distilled down to [3] the known pathogenic BRCA mutations cohort (n=196). Each cohort was analyzed independently yielding significant progression free survival (PFS) improvements across all three levels of inclusion. As hypothesized, more impressive outcomes were seen with more impressive BRCA aberrations. As of this report there were <1/3 of the number of deaths needed to conduct overall survival analyses, so that verdict is still out. But we all know it’s better down where it’s wetter, and we bet the final survival outcomes of ARIEL3 will be more than a drop in the bucket of promising BRCA-deranged responses to PARP inhibition.