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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-03003-9

摘要内容如下：

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改善了晚期卵巢癌妇女的无进展生存期。然而，并不是所有的PARP抑制剂都能为未选择生物标志物的人群提供益处。Senaparib是一种PARP抑制剂，在一期研究中，其在实体瘤（包括卵巢癌）患者中表现出抗肿瘤活性。该多中心、双盲、3期试验将404名患有晚期卵巢癌（国际妇产科联合会III-IV期）且对一线以铂为基础的化疗有反应的女性患者随机（2:1）给予塞那帕尼100mg（n=271）或安慰剂（n=133），每日一次口服，持续2年主要终点是通过盲法独立中心审查评估的无进展生存期。在预先指定的中期分析中，塞那帕尼组未达到中位无进展生存期，而安慰剂组为13.6个月（风险比0.43，95%置信区间0.32-0.58；P<0.0001）。在由BRCA1和BRCA2突变或同源重组状态定义的亚组中，塞那帕尼相对于安慰剂的益处是一致的。179例（66%）和27例（20%）患者分别发生了≥3级治疗中出现的不良事件。与安慰剂相比，塞那帕尼显著改善了一线铂类化疗有效的晚期卵巢癌患者的无进展生存期，与BRCA1和BRCA2突变状态无关，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。这些结果支持塞那帕尼作为一线化疗有效的晚期卵巢癌患者的维持治疗。ClinicalTrials.gov标识符：NCT04169997。

英文原文如下：

Abstracts

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 .

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