{Reference Type}: Journal Article
{Title}: Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial.
{Author}: Wu X;Liu J;Wang J;Wang L;Lin Z;Wang X;Zhu J;Kong B;Fei J;Tang Y;Xia B;Liang Z;Wang K;Huang Y;Zheng H;Lin A;Jiang K;Wang W;Wang X;Lou G;Pan H;Yao S;Li G;Hao M;Cai Y;Chen X;Yang Z;Chen Y;Wen H;Qu P;Xu C;Hsieh CY; ;
{Journal}: Nat Med
{Volume}: 30
{Issue}: 6
{Year}: 2024 Jun 15
{Factor}: 87.241
{DOI}: 10.1038/s41591-024-03003-9
{Abstract}: Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as maintenance therapy after first-line chemotherapy have improved progression-free survival in women with advanced ovarian cancer; however, not all PARP inhibitors can provide benefit for a biomarker-unselected population. Senaparib is a PARP inhibitor that demonstrated antitumor activity in patients with solid tumors, including ovarian cancer, in phase 1 studies. The multicenter, double-blind, phase 3 trial FLAMES randomized (2:1) 404 females with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III-IV) and response to first-line platinum-based chemotherapy to senaparib 100 mg (n = 271) or placebo (n = 133) orally 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 was not reached with senaparib and was 13.6 months with placebo (hazard ratio 0.43, 95% confidence interval 0.32-0.58; P < 0.0001). The benefit with senaparib over placebo was consistent in the subgroups defined by BRCA1 and BRCA2 mutation or homologous recombination status. Grade ≥3 treatment-emergent adverse events occurred in 179 (66%) and 27 (20%) patients, respectively. Senaparib significantly improved progression-free survival versus placebo in patients with advanced ovarian cancer after response to first-line platinum-based chemotherapy, irrespective of BRCA1 and BRCA2 mutation status and with consistent benefits observed between homologous recombination subgroups, and was well tolerated. These results support senaparib as a maintenance treatment for patients with advanced ovarian cancer after a response to first-line chemotherapy. ClinicalTrials.gov identifier: NCT04169997 .