在新诊断的晚期高级别卵巢癌患者中维持奥拉帕利联合贝伐珠单抗：III 期 PAOLA-1/ENGOT-ov25 试验中第二次无进展生存的主要分析。
Maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced high-grade ovarian cancer: Main analysis of second progression-free survival in the phase III PAOLA-1/ENGOT-ov25 trial.
机构信息
Grupo Español de Investigación en Cáncer de Ovario (GEICO), Spain and MD Anderson Cancer Center Madrid, Spain.
Centre Hospitalier Régional Universitaire de Lille, Lille, and Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), France.
出版信息
Eur J Cancer. 2022 Oct;174:221-231. doi: 10.1016/j.ejca.2022.07.022. Epub 2022 Sep 5.
BACKGROUND
PAOLA-1/ENGOT-ov25 (NCT02477644) demonstrated a significant progression-free survival (PFS) benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab in newly diagnosed, advanced ovarian cancer. We report the prespecified main second progression-free survival (PFS2) analysis for PAOLA-1.
METHODS
This randomised, double-blind, phase III trial was conducted in 11 countries. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were in response after first-line platinum-based chemotherapy plus bevacizumab. Patients were randomised 2:1 to olaparib (300 mg twice daily) or placebo for up to 24 months; all patients received bevacizumab (15 mg/kg every 3 weeks) for up to 15 months. Primary PFS end-point was reported previously. Time from randomisation to second disease progression or death was a key secondary end-point included in the hierarchical-testing procedure.
RESULTS
After a median follow-up of 35.5 months and 36.5 months, respectively, median PFS2 was 36.5 months (olaparib plus bevacizumab) and 32.6 months (placebo plus bevacizumab), hazard ratio 0.78; 95% confidence interval (CI) 0.64-0.95; P = 0.0125. Median time to second subsequent therapy or death was 38.2 months (olaparib plus bevacizumab) and 31.5 months (placebo plus bevacizumab), hazard ratio 0.78; 95% CI 0.64-0.95; P = 0.0115. Seventy-two (27%) patients in the placebo plus bevacizumab group received a poly(ADP-ribose) polymerase inhibitor as first subsequent therapy. No new safety signals were observed for olaparib plus bevacizumab.
CONCLUSION
In newly diagnosed, advanced ovarian cancer, maintenance olaparib plus bevacizumab provided continued benefit beyond first progression, with a significant PFS2 improvement and a time to second subsequent therapy or death delay versus placebo plus bevacizumab.
背景
PAOLA-1/ENGOT-ov25（NCT02477644）研究显示，在新诊断的晚期卵巢癌患者中，与安慰剂联合贝伐珠单抗相比，奥拉帕利维持治疗联合贝伐珠单抗可显著改善无进展生存期（PFS）。本研究报告了 PAOLA-1 的预设主要次要无进展生存期（PFS2）分析结果。
方法
这是一项在 11 个国家进行的随机、双盲、III 期临床试验。纳入的患者为新诊断的晚期高级别卵巢癌患者，在接受一线含铂化疗联合贝伐珠单抗治疗后有缓解。患者以 2:1 的比例随机分组，分别接受奥拉帕利（300mg，每日两次）或安慰剂治疗，最长 24 个月；所有患者均接受贝伐珠单抗（15mg/kg，每 3 周一次）治疗，最长 15 个月。主要 PFS 终点此前已报道。随机分组至第二次疾病进展或死亡的时间是分层检验程序中的关键次要终点。
结果
中位随访 35.5 个月和 36.5 个月时，奥拉帕利联合贝伐珠单抗组和安慰剂联合贝伐珠单抗组的中位 PFS2 分别为 36.5 个月和 32.6 个月，风险比为 0.78；95%置信区间（CI）为 0.64-0.95；P=0.0125。奥拉帕利联合贝伐珠单抗组和安慰剂联合贝伐珠单抗组中位时间至第二次后续治疗或死亡分别为 38.2 个月和 31.5 个月，风险比为 0.78；95%CI 为 0.64-0.95；P=0.0115。安慰剂联合贝伐珠单抗组有 72 例（27%）患者接受了聚（ADP-核糖）聚合酶抑制剂作为首次后续治疗。奥拉帕利联合贝伐珠单抗组未观察到新的安全性信号。
结论
在新诊断的晚期卵巢癌患者中，与安慰剂联合贝伐珠单抗相比，奥拉帕利维持治疗联合贝伐珠单抗在首次进展后仍能持续获益，可显著改善 PFS2，并延迟第二次后续治疗或死亡时间。
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