Introduction: This randomized phase II trial aimed at evaluating the engineered programmed cell death ligand 1 (PD‐L1) antibody atezolizumab in SCLC progressing after first‐line platinum–etoposide chemotherapy. Methods: Patients were randomized 2:1 to atezolizumab (1200 mg intravenously every 3 weeks) until progression or unacceptable toxicity, or conventional chemotherapy (up to 6 cycles of topotecan or re‐induction of initial chemotherapy). Patients were not selected based on PD‐L1 tissue expression. The primary endpoint was objective response rate at 6 weeks. A two‐stage design with 2:1 randomization and O'Brien‐Fleming stopping rules was used. The null hypothesis was rejected if more than 12 of 45 patients were responders. Results: Overall, 73 patients were randomized (atezolizumab n = 49; chemotherapy n = 24). At 6 weeks, 1 of 43 eligible atezolizumab patients achieved an objective response (2.3%, 95% confidence interval [CI]: 0.0–6.8), whereas 8 others had stable disease (20.9% disease control rate; 95% CI: 8.8–33.1). Among eligible chemotherapy patients (n = 20), 10% achieved an objective response (65% disease control rate). Median progression‐free survival was 1.4 months (95% CI: 1.2–1.5) with atezolizumab and 4.3 months (95% CI: 1.5–5.9) with chemotherapy. Overall survival did not significantly differ between groups. Median overall survival was 9.5 months versus 8.7 months for the atezolizumab and the chemotherapy group, respectively (adjusted hazard ratioatezolizumab: 0.84, 95% CI: 0.45–1.58; p = 0.60). Two atezolizumab patients (4.2%) experienced grade 3 fatigue, and two others grade 1 dysthyroidism. Among 53 evaluable specimens, only 1 (2%) had positive immunohistochemical PD‐L1 staining (SP142 clone). Conclusions: Atezolizumab monotherapy in relapsed SCLC failed to show significant efficacy. No unexpected safety concerns were observed.

中文翻译：

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抗程序性细胞死亡配体 1 Atezolizumab 或化疗作为小细胞肺癌患者二线治疗的随机非比较 2 期研究：IFCT-1603 试验的结果

简介：这项随机 II 期试验旨在评估工程化程序性细胞死亡配体 1 (PD-L1) 抗体 atezolizumab 在一线铂-依托泊苷化疗后进展的 SCLC 中的作用。方法：患者以 2:1 的比例随机分配至 atezolizumab（每 3 周静脉注射 1200 mg）直至疾病进展或出现不可接受的毒性，或常规化疗（最多 6 个周期的拓扑替康或重新诱导初始化疗）。患者不是根据 PD-L1 组织表达选择的。主要终点是 6 周时的客观反应率。使用具有 2:1 随机化和 O'Brien-Fleming 停止规则的两阶段设计。如果 45 名患者中有超过 12 名是响应者，则拒绝原假设。结果：总共有 73 名患者被随机分组​​（atezolizumab n = 49；化疗 n = 24）。在第 6 周时，43 名符合条件的 atezolizumab 患者中有 1 名达到客观缓解（2.3%，95% 置信区间 [CI]：0.0-6.8），而另外 8 名患者病情稳定（20.9% 疾病控制率；95% CI：8.8-33.1）。在符合条件的化疗患者（n = 20）中，10% 达到了客观反应（65% 的疾病控制率）。Atezolizumab 组的中位无进展生存期为 1.4 个月（95% CI：1.2-1.5），化疗组为 4.3 个月（95% CI：1.5-5.9）。组间总生存期没有显着差异。Atezolizumab 和化疗组的中位总生存期分别为 9.5 个月和 8.7 个月（调整后的风险比值atezolizumab：0.84，95% CI：0.45–1.58；p = 0.60）。两名 atezolizumab 患者 (4.2%) 出现 3 级疲劳，另外两名患者出现 1 级甲状腺功能减退。在 53 个可评价标本中，只有 1 个 (2%) 具有阳性免疫组织化学 PD-L1 染色（SP142 克隆）。结论： Atezolizumab 单药治疗复发性 SCLC 未能显示出显着疗效。没有观察到意外的安全问题。