University of New South Wales Clinical School, Prince of Wales Hospital, Randwick, NSW, Australia.
Dana-Farber Cancer Institute, Boston, MA, USA.
Br J Cancer. 2018 Oct;119(9):1075-1085. doi: 10.1038/s41416-018-0271-y. Epub 2018 Oct 24.
In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer.
Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79% maturity) data, from the last data cut-off (9 May 2016).
Thirty-two patients (24%) received maintenance olaparib for over 2 years; 15 (11%) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6%). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95% confidence interval 0.55‒0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met.
Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented long-term benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients.
在研究 19 中，与安慰剂相比，奥拉帕利维持单药治疗可显著延长铂类敏感、复发性高级别浆液性卵巢癌患者的无进展生存期。
研究 19 是一项随机、安慰剂对照、II 期临床试验，纳入了 265 名患者，这些患者至少接受过两种铂类化疗方案，且对最近的治疗方案有完全或部分缓解。患者被随机分配至奥拉帕利（胶囊；400mg，bid）或安慰剂组。我们报告了来自最后一次数据截止（2016 年 5 月 9 日）的长期安全性和最终成熟的总生存期（OS；79%成熟度）数据。
32 名患者（24%）接受奥拉帕利维持治疗超过 2 年；15 名患者（11%）接受维持治疗超过 6 年。长期治疗未发现新的耐受性信号，且不良事件通常为低级别。因不良事件而停药的发生率较低（6%）。与安慰剂相比，奥拉帕利观察到 OS 有明显优势（风险比 0.73，95%置信区间 0.55‒0.95，P=0.02138），无论 BRCA1/2 突变状态如何，但未达到统计学意义的预设阈值。
研究 19 显示，无论 BRCA1/2 突变状态如何，最终 OS 结果均有利，且奥拉帕利维持治疗对铂类敏感、复发性卵巢癌患者亚组具有前所未有的长期获益。
