Istituto Tumori Milano + Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
Catholic University of Sacred Heart, Milan, Italy.
Int J Gynecol Cancer. 2024 Apr 1;34(4):550-558. doi: 10.1136/ijgc-2023-004995.
OBJECTIVE: In the PAOLA-1/ENGOT-ov25 trial (NCT02477644), adding maintenance olaparib to bevacizumab provided a substantial progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and homologous recombination deficiency (HRD)-positive tumors, irrespective of clinical risk. Subsequently, a clinically meaningful improvement in overall survival was reported with olaparib plus bevacizumab in the HRD-positive subgroup. We report updated progression-free survival and overall survival by clinical risk and HRD status. METHODS: Patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab received maintenance olaparib (up to 24 months) plus bevacizumab (up to 15 months in total) or placebo plus bevacizumab. This analysis evaluated 5-year progression-free survival and mature overall survival in patients classified by clinical risk and HRD status. RESULTS: Of 806 randomized patients, 74% were higher-risk and 26% were lower-risk. In higher-risk HRD-positive patients, the hazard ratio (HR) for progression-free survival was 0.46 (95% confidence interval (95% CI) 0.34 to 0.61), with 5-year progression-free survival of 35% with olaparib plus bevacizumab versus 15% with bevacizumab alone; and the HR for overall survival was 0.70 (95% CI 0.50 to 1.00), with 5-year overall survival of 55% versus 42%, respectively. In lower-risk HRD-positive patients, the HR for progression-free survival was 0.26 (95% CI 0.15 to 0.45), with 5-year progression-free survival of 72% with olaparib plus bevacizumab versus 28% with bevacizumab alone; and the HR for overall survival was 0.31 (95% CI 0.14 to 0.66), with 5-year overall survival of 88% versus 61%, respectively. No benefit was seen in HRD-negative patients regardless of clinical risk. CONCLUSION: This analysis indicates that in patients with newly diagnosed advanced HRD-positive ovarian cancer, maintenance olaparib plus bevacizumab should not be limited to those considered at higher risk of disease progression. Five-year progression-free survival rates support long-term remission and suggest an increased potential for cure with particular benefit suggested in lower-risk HRD-positive patients.
目的：在 PAOLA-1/ENGOT-ov25 试验（NCT02477644）中，与贝伐珠单抗单药治疗相比，新诊断的晚期卵巢癌和同源重组缺陷（HRD）阳性肿瘤患者在接受一线含铂化疗联合贝伐珠单抗治疗后加用维持奥拉帕利治疗可显著延长无进展生存期，无论临床风险如何。随后，在 HRD 阳性亚组中，奥拉帕利联合贝伐珠单抗显示出具有临床意义的总生存期改善。我们报告了按临床风险和 HRD 状态分层的无进展生存期和总生存期的最新数据。
方法：一线含铂化疗联合贝伐珠单抗治疗后有临床缓解的患者接受奥拉帕利维持治疗（最长 24 个月）联合贝伐珠单抗（最长 15 个月）或安慰剂联合贝伐珠单抗治疗。这项分析评估了按临床风险和 HRD 状态分类的患者 5 年无进展生存期和成熟总生存期。
结果：在 806 例随机患者中，74%为高风险，26%为低风险。在高风险 HRD 阳性患者中，无进展生存期的风险比（HR）为 0.46（95%置信区间（95%CI）为 0.34 至 0.61），奥拉帕利联合贝伐珠单抗组 5 年无进展生存率为 35%，而贝伐珠单抗单药组为 15%；总生存期的 HR 为 0.70（95%CI 为 0.50 至 1.00），奥拉帕利联合贝伐珠单抗组 5 年总生存率为 55%，贝伐珠单抗单药组为 42%。在低风险 HRD 阳性患者中，无进展生存期的 HR 为 0.26（95%CI 为 0.15 至 0.45），奥拉帕利联合贝伐珠单抗组 5 年无进展生存率为 72%，贝伐珠单抗单药组为 28%；总生存期的 HR 为 0.31（95%CI 为 0.14 至 0.66），奥拉帕利联合贝伐珠单抗组 5 年总生存率为 88%，贝伐珠单抗单药组为 61%。无论临床风险如何，HRD 阴性患者均未观察到获益。
结论：这项分析表明，对于新诊断的晚期 HRD 阳性卵巢癌患者，维持奥拉帕利联合贝伐珠单抗不应仅限于那些被认为疾病进展风险较高的患者。5 年无进展生存率支持长期缓解，并提示对于低风险 HRD 阳性患者具有增加的治愈潜力，带来特别获益。
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