Multicenter phase 3 trial of senaparib as first-line maintenance therapy in advanced ovarian cancer

PARP inhibitors as maintenance therapy after first-line chemotherapy have improved progression-free survival in women with advanced ovarian cancer (aOC); however, not all PARP inhibitors can provide benefit for a biomarker-unselected population. The multicenter phase 3 FLAMES trial randomized 404 women with aOC (stage III-IV) after response to first-line platinum-based chemotherapy 2:1 to senaparib 100 mg or placebo once daily for up to 2 years. The primary endpoint was progression-free survival assessed by blinded independent central review. At the prespecified interim analysis, the median progression-free survival (primary endpoint) was not reached with senaparib and was 13.6 months with placebo (HR 0.43; p<0.0001). The benefit with senaparib over placebo was consistent in subgroups defined by BRCA1 and BRCA2 mutation of homologous recombination status. Grade ≥3 treatment-emergent adverse events occurred in 66% and 20%, respectively. The authors conclude that senaparib significantly improved PFS versus placebo in patients with aOC after response to first-line chemotherapy, irrespective of BRCA1 and BRCA2 mutation status and with consistent benefits observed between homologous recombination subgroups, and was well tolerated.