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.

聚（腺苷二磷酸核糖）聚合酶（PARP）抑制剂作为一线化疗后的维持治疗可改善晚期卵巢癌女性的无进展生存期；然而，并非所有 PARP 抑制剂都能为未选择生物标志物的人群带来益处。 Senaparib 是一种 PARP 抑制剂，在 1 期研究中显示出对实体瘤（包括卵巢癌）患者具有抗肿瘤活性。多中心、双盲、3 期试验 FLAMES 对 404 名晚期卵巢癌（国际妇产科联合会 III-IV 期）女性进行随机 (2:1) 分组，这些女性对一线铂类化疗对 senaparib 100 mg 有反应（n  = 271) 或安慰剂 ( n  = 133) 每天口服一次，持续长达 2 年。主要终点是通过盲法独立中央审查评估的无进展生存期。在预先指定的中期分析中，塞纳帕尼组未达到中位无进展生存期，安慰剂组为 13.6 个月（风险比 0.43，95% 置信区间 0.32–0.58；P  < 0.0001）。在BRCA1和BRCA2突变或同源重组状态定义的亚组中，senaparib 相对于安慰剂的益处是一致的。分别有 179 名 (66%) 和 27 名 (20%) 患者发生了 3 级以上的治疗相关不良事件。与安慰剂相比，Senaparib 显着改善了晚期卵巢癌患者对一线铂类化疗有反应后的无进展生存期，无论BRCA1和BRCA2突变状态如何，并且在同源重组亚组之间观察到一致的益处，并且耐受性良好。这些结果支持塞纳帕尼作为对一线化疗有反应的晚期卵巢癌患者的维持治疗。 ClinicalTrials.gov 标识符：NCT04169997。