Department of Pulmonary and Critical Care Medicine, Xingtai Third Hospital, Xingtai, Hebei, China.
Clin Respir J. 2024 Nov;18(11):e70032. doi: 10.1111/crj.70032.
Small cell lung cancer (SCLC) is one of the most lethal malignancies worldwide. This study aimed to examine the clinical benefits of new systemic therapies derived from randomized controlled trials (RCTs) published from 2002 to 2023 based on the magnitude of clinical benefit scale developed by the European Society for Medical Oncology (ESMO-MCBS).
We searched PubMed for Phase 3 RCTs on systemic therapy for SCLC published between January 2002 and December 2023. Therapeutic benefit was graded from 5 to 1 according to the ESMO-MCBS framework, with a score of 4 or 5 representing a meaningful clinical benefit. The statistical power of the trial design was also assessed using ESMO-MCBS.
Sixty-four RCTs with 23 683 participants were eligible for inclusion. The number of RCTs related to molecular targeted therapy or immunotherapy has increased over the years. Among the 62 RCTs for which statistical power could be evaluated, 38 (61.3%) were designed to identify an effect size that would meet the ESMO-MCBS benefit threshold and were less likely to investigate second- or subsequent-line treatment (15.8% vs. 50.0%, p = 0.004), have noninferiority design (0% vs. 25.0%, p = 0.002) and set PFS (0% vs. 16.7%) or response rate (0% vs. 16.7%) as the only primary endpoint (p = 0.002). The ESMO-MCBS framework was applied in 29 RCTs reporting positive results, and only 8 (27.6%) met the threshold for a clinical benefit. The RCTs designed to detect differences that would meet the thresholds were more likely to demonstrate meaningful clinical benefit (87.5% vs. 50.0%, p = 0.099).
Most positive SCLC-RCTs did not meet the ESMO-MCBS threshold for meaningful clinical benefits. Strict power calculations should be adopted in the design of future RCTs.
小细胞肺癌（SCLC）是全球最致命的恶性肿瘤之一。本研究旨在根据欧洲肿瘤内科学会（ESMO-MCBS）制定的临床获益量表，评估 2002 年至 2023 年期间发表的随机对照试验（RCT）中新型系统治疗的临床获益。
我们在 PubMed 上检索了 2002 年 1 月至 2023 年 12 月期间发表的 SCLC 系统治疗的 III 期 RCT。根据 ESMO-MCBS 框架，将治疗益处从 5 级到 1 级分级，得分 4 或 5 表示有意义的临床获益。还使用 ESMO-MCBS 评估了试验设计的统计功效。
共有 64 项 RCT 和 23683 名参与者符合纳入标准。与分子靶向治疗或免疫治疗相关的 RCT 数量逐年增加。在可评估统计功效的 62 项 RCT 中，38 项（61.3%）旨在确定符合 ESMO-MCBS 获益阈值的效应大小，并且不太可能研究二线或后续治疗（15.8%比 50.0%，p=0.004），具有非劣效性设计（0%比 25.0%，p=0.002），并将 PFS（0%比 16.7%）或反应率（0%比 16.7%）作为唯一的主要终点（p=0.002）。29 项报告阳性结果的 RCT 应用了 ESMO-MCBS 框架，只有 8 项（27.6%）符合临床获益阈值。旨在检测符合阈值差异的 RCT 更有可能显示出有意义的临床获益（87.5%比 50.0%，p=0.099）。
大多数 SCLC-RCT 的阳性结果并未达到 ESMO-MCBS 有意义的临床获益阈值。未来 RCT 的设计应采用严格的功效计算。
