University of Sheffield, Sheffield, United Kingdom; Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.
Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom.
Lung Cancer. 2022 Sep;171:26-33. doi: 10.1016/j.lungcan.2022.07.007. Epub 2022 Jul 15.
Small cell lung cancer (SCLC) responds well to chemoradiotherapy but frequently relapses. Here, we evaluate activity and safety of the poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitor olaparib as maintenance treatment for patients with chemoresponsive SCLC.
Eligible patients had complete or partial response to first line chemotherapy or chemoradiotherapy for SCLC. Patients were randomised 2:2:1:1 to olaparib 300 mg twice a day (BD), olaparib 200 mg three times a day (TDS), placebo BD or placebo TDS. The primary outcome was progression-free survival time (PFS). The trial design had 80% power to detect a 3-month difference in median PFS based on a one-sided 5% significance level. Secondary outcome measures included overall survival time (OS), adverse events and quality of life. ISRCTN 73164486, EudraCT 2010-021165-76.
220 patients were randomised: 74 placebo, 73 olaparib BD, 73 olaparib TDS. Median PFS (90% confidence interval (CI)) was 2·5 (1·8, 3·7), 3·7 (3·1, 4·6) and 3·6 (2·8, 4·7) months in the placebo, olaparib BD and TDS arms, respectively. There was no significant difference in PFS between olaparib and placebo for either BD (Hazard Ratio (HR) (90%CI) 0·76 (0·57, 1·02), P = 0·125 or TDS 0·86, (0·64, 1·15), P = 0·402. Common adverse events on olaparib were fatigue, nausea, anaemia, vomiting and anorexia. Of 214 patients who discontinued treatment before 24 months, toxicity was the reason cited for 66 (18 placebo, 24 olaparib BD, 24 olaparib TDS).
This trial does not provide sufficient evidence that either the BD or TDS regimen for maintenance olaparib monotherapy improves PFS or OS in an unselected SCLC population to warrant further research. Toxicity for olaparib was similar to other studies.
小细胞肺癌 (SCLC) 对放化疗反应良好，但常复发。在此，我们评估聚（二磷酸腺苷-核糖）聚合酶 (PARP) 抑制剂奥拉帕利作为对化疗有反应的 SCLC 患者的维持治疗的活性和安全性。
符合条件的患者对 SCLC 的一线化疗或放化疗有完全或部分缓解。患者按 2:2:1:1 的比例随机分配至奥拉帕利 300mg 每日两次 (BD)、奥拉帕利 200mg 每日三次 (TDS)、BD 安慰剂或 TDS 安慰剂。主要终点为无进展生存期 (PFS)。试验设计有 80%的功效，可根据单侧 5%显著性水平检测中位 PFS 差异 3 个月。次要终点包括总生存期 (OS)、不良事件和生活质量。ISRCTN73164486，EudraCT2010-021165-76。
220 名患者被随机分配：74 名安慰剂，73 名奥拉帕利 BD，73 名奥拉帕利 TDS。安慰剂、奥拉帕利 BD 和 TDS 组的中位 PFS（90%置信区间 (CI)）分别为 2.5（1.8，3.7）、3.7（3.1，4.6）和 3.6（2.8，4.7）个月。BD 组（HR（90%CI）0.76（0.57，1.02），P=0.125）或 TDS 组（HR0.86，0.64，1.15），P=0.402）奥拉帕利与安慰剂相比，PFS 无显著差异。奥拉帕利常见的不良反应有疲劳、恶心、贫血、呕吐和厌食。在 24 个月前停止治疗的 214 名患者中，有 66 名（18 名安慰剂、24 名奥拉帕利 BD、24 名奥拉帕利 TDS）因毒性而停药。
本试验并未提供足够的证据表明奥拉帕利 BD 或 TDS 方案用于维持治疗可改善未经选择的 SCLC 人群的无进展生存期或总生存期，因此不值得进一步研究。奥拉帕利的毒性与其他研究相似。
