Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial
Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial
复制标题
DOI：
10.1016/s1470-2045(21)00531-3
复制
发表时间：
2021-11-29
期刊：
影响因子：
51.1
通讯作者：
DiSilvestro, Paul
中科院分区：
文献类型：
--
作者：
Banerjee, Susana;Moore, Kathleen N.;DiSilvestro, Paul
背景：对于新诊断的晚期卵巢癌患者，增加长期缓解机会和可能治愈的治疗方案存在高度未满足的需求。在SOLO 1/GOG 3004的主要分析中，与安慰剂相比，聚（ADP-核糖）聚合酶（PARP）抑制剂olaparib显著改善了BRCA突变患者的无进展生存期;未达到中位无进展生存期。在这里，我们报告一个更新的，事后分析的无进展生存SOLO 1，经过5年的following.Methods SOLO 1是一个随机，双盲，安慰剂对照，3期临床试验，在118个中心在15个国家，招募患者年龄18岁或以上，东部肿瘤协作组的性能状态0-1和BRCA突变，新诊断，晚期，高级别浆液性或类浆液性卵巢癌，在铂类化疗后有完全或部分临床反应。患者通过基于网络或交互式语音应答系统随机分配（2：1）接受奥拉帕尼（300 mg，每日两次）或安慰剂片剂口服作为维持单药治疗，最长2年;随机化按区组进行，并根据铂类化疗后的临床应答进行分层。患者、治疗提供者和数据评估者均对分组设盲。主要终点是评估者评估的无进展生存期。在意向治疗人群中报告疗效，在接受至少一剂治疗的患者中报告安全性。本次更新的事后分析的数据截止日期为2020年3月5日。该试验注册于ClinicalTrials.gov（NCT 01844986），目前正在进行中，但不接受新的参与者。中位治疗持续时间为24.6个月（IQR 11. 2-24奥拉帕尼组中位随访时间为4.8年（2.8-5.3），安慰剂组中位随访时间为5.0年（2.6-5.3）。在这项事后分析中，奥拉帕尼组的中位无进展生存期为56.0个月（95% CI 41.9-未达到），安慰剂组为13.8个月（11.1-18.2）（风险比0.33 [95% CI 0.25-0.43]）。最常见的3-4级不良事件是贫血（57122%）和中性粒细胞减少症（22 [8%] vs 6 [5%]），严重不良事件发生在奥拉帕尼组55/260（21%）和安慰剂组17/130（13%）。研究治疗期间或停药后30天内发生的治疗相关不良事件均未报告为导致死亡。自主要数据截止日期以来，包括30天安全性随访期后，未报告其他骨髓增生异常综合征或急性髓性白血病病例。解释对于新诊断的晚期卵巢癌和BRCA突变患者，据我们所知，在对PARP抑制剂的任何随机对照试验进行最长随访后，奥拉帕尼2年维持治疗的益处在治疗结束后仍持续，使中位无进展生存期延长至4.5年。这些结果支持在这种情况下使用奥拉帕尼作为标准治疗。版权所有（C）2021爱思唯尔有限公司保留所有权利。
Background There is a high unmet need for treatment regimens that increase the chance of long-term remission and possibly cure for women with newly diagnosed advanced ovarian cancer. In the primary analysis of SOLO1/GOG 3004, the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib significantly improved progression-free survival versus placebo in patients with a BRCA mutation; median progression-free survival was not reached. Here, we report an updated, post-hoc analysis of progression-free survival from SOLO1, after 5 years of follow-up.Methods SOLO1 was a randomised, double-blind, placebo-controlled, phase 3 trial, done across 118 centres in 15 countries, that enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1 and with BRCA-mutated, newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer with a complete or partial clinical response after platinum-based chemotherapy. Patients were randomly assigned (2:1) via a web-based or interactive voice-response system to receive olaparib (300 mg twice daily) or placebo tablets orally as maintenance monotherapy for up to 2 years; randomisation was by blocks and was stratified according to clinical response after platinum-based chemotherapy. Patients, treatment providers, and data assessors were masked to group assignment. The primary endpoint was investigator-assessed progression-free survival. Efficacy is reported in the intention-to-treat population and safety in patients who received at least one dose of treatment. The data cutoff for this updated, post-hoc analysis was March 5, 2020. This trial is registered with ClinicalTrials.gov (NCT01844986) and is ongoing but closed to new participants.Findings Between Sept 3,2013, and March 6,2015,260 patients were randomly assigned to olaparib and 131 to placebo. The median treatment duration was 24.6 months (IQR 11. 2-24 9) in the olaparib group and 13.9 months (8.0-24.8) in the placebo group; median follow-up was 4.8 years (2.8-5.3) in the olaparib group and 5.0 years (2.6-5.3) in the placebo group. In this post-hoc analysis, median progression-free survival was 56.0 months (95% CI 41.9-not reached) with olaparib versus 13.8 months (11.1-18.2) with placebo (hazard ratio 0.33 [95% CI 0.25-0.43]). The most common grade 3-4 adverse events were anaemia (57 122%] of 260 patients receiving olaparib vs two 12.degrees 4] of 130 receiving placebo) and neutropenia (22 [8%] vs six [5%]), and serious adverse events occurred in 55 (21%) of 260 patients in the olaparib group and 17 (13%) of 130 in the placebo group. No treatment-related adverse events that occurred during study treatment or up to 30 days after discontinuation were reported as leading to death. No additional cases of myelodysplastic syndrome or acute myeloid leukaemia were reported since the primary data cutoff, including after the 30-day safety follow-up period.Interpretation For patients with newly diagnosed advanced ovarian cancer and a BRCA mutation, after, to our knowledge, the longest follow-up for any randomised controlled trial of a PARP inhibitor in this setting, the benefit derived from 2 years' maintenance therapy with olaparib was sustained beyond the end of treatment, extending median progression-free survival past 4.5 years. These results support the use of maintenance olaparib as a standard of care in this setting. Copyright (C) 2021 Elsevier Ltd. All rights reserved.