Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial.
Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial.
复制标题
DOI：
10.1200/jco.22.01549
复制
发表时间：
2023-01-20
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
在SOLO1/GOG 3004 （ClinicalTrials.gov标识号：NCT01844986）中，poly（adp -核糖）聚合酶抑制剂olaparib的维持治疗为新诊断的晚期卵巢癌和BRCA1和/或BRCA2 （BRCA）突变患者提供了持续的无进展生存获益。我们报告了7年随访后的总生存期（OS），这是临床相关的时间点，也是一线多聚（adp -核糖）聚合酶抑制剂最长的随访时间。这项双盲III期试验将新诊断的晚期卵巢癌和BRCA突变患者随机分配到维持奥拉帕尼（n = 260）或安慰剂（n = 131），为期2年。在7年的随访后，对OS进行了预先指定的描述性分析，这是一个次要终点。奥拉帕尼组和安慰剂组的中位治疗时间分别为24.6个月和13.9个月，中位随访时间分别为88.9个月和87.4个月。OS的风险比为0.55 （95% CI, 0.40 ~ 0.76; P = 0.0004 [P < 0.0001才有统计学意义]）。在7年时，67.0%的奥拉帕尼患者和46.5%的安慰剂患者存活，45.3%和20.6%的患者存活且未接受首次后续治疗（Kaplan-Meier估计）。骨髓增生异常综合征和急性髓系白血病的发病率仍然很低，治疗组之间的新发原发性恶性肿瘤保持平衡。结果表明，在新诊断的晚期卵巢癌和BRCA突变患者中，维持性奥拉帕尼的OS改善具有临床意义，尽管根据预先规定的标准没有统计学意义，并支持在这种情况下使用维持性奥拉帕尼实现长期缓解；治愈的可能性也可能得到提高。在长期随访中未观察到新的安全信号。
In SOLO1/GOG 3004 (ClinicalTrials.gov identifier: NCT01844986), maintenance therapy with the poly(ADP-ribose) polymerase inhibitor olaparib provided a sustained progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 (BRCA) mutation. We report overall survival (OS) after a 7-year follow-up, a clinically relevant time point and the longest follow-up for any poly(ADP-ribose) polymerase inhibitor in the first-line setting. This double-blind phase III trial randomly assigned patients with newly diagnosed advanced ovarian cancer and a BRCA mutation in clinical response to platinum-based chemotherapy to maintenance olaparib (n = 260) or placebo (n = 131) for up to 2 years. A prespecified descriptive analysis of OS, a secondary end point, was conducted after a 7-year follow-up. The median duration of treatment was 24.6 months with olaparib and 13.9 months with placebo, and the median follow-up was 88.9 and 87.4 months, respectively. The hazard ratio for OS was 0.55 (95% CI, 0.40 to 0.76; P = .0004 [P < .0001 required to declare statistical significance]). At 7 years, 67.0% of olaparib patients versus 46.5% of placebo patients were alive, and 45.3% versus 20.6%, respectively, were alive and had not received a first subsequent treatment (Kaplan-Meier estimates). The incidence of myelodysplastic syndrome and acute myeloid leukemia remained low, and new primary malignancies remained balanced between treatment groups. Results indicate a clinically meaningful, albeit not statistically significant according to prespecified criteria, improvement in OS with maintenance olaparib in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation and support the use of maintenance olaparib to achieve long-term remission in this setting; the potential for cure may also be enhanced. No new safety signals were observed during long-term follow-up.