抗程序性细胞死亡配体 1 阿特珠单抗或化疗作为小细胞肺癌二线治疗的随机非对照 II 期研究：IFCT-1603 试验结果。
A Randomized Non-Comparative Phase II Study of Anti-Programmed Cell Death-Ligand 1 Atezolizumab or Chemotherapy as Second-Line Therapy in Patients With Small Cell Lung Cancer: Results From the IFCT-1603 Trial.
机构信息
Department of Thoracic Oncology, Montpellier Regional University Hospital, Montpellier, France.
Department of Multidisciplinary Oncology and Therapeutic Innovations, Assistance Publique - Hôpitaux de Marseille, Aix Marseille University, Marseille, France.
出版信息
J Thorac Oncol. 2019 May;14(5):903-913. doi: 10.1016/j.jtho.2019.01.008. Epub 2019 Jan 18.
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 ratio : 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.
简介
本随机 II 期试验旨在评估在一线铂类依托泊苷化疗后进展的 SCLC 患者中使用工程化程序性死亡配体 1（PD-L1）抗体阿特珠单抗的疗效。
方法
患者按 2:1 随机分为阿特珠单抗（1200mg 静脉注射，每 3 周一次）组或常规化疗组（最多 6 个周期的拓扑替康或重新诱导初始化疗），直至疾病进展或出现不可接受的毒性。患者未根据 PD-L1 组织表达进行选择。主要终点为 6 周时的客观缓解率。采用两阶段设计，2:1 随机分组和 O'Brien-Fleming 停止规则。如果 45 例患者中超过 12 例有缓解，则拒绝零假设。
结果
共有 73 例患者随机分组（阿特珠单抗组 n=49；化疗组 n=24）。6 周时，43 例符合条件的阿特珠单抗患者中，1 例（2.3%，95%置信区间[CI]：0.0-6.8）达到客观缓解，另外 8 例为疾病稳定（20.9%的疾病控制率；95%CI：8.8-33.1）。20 例符合条件的化疗患者中，10%（65%的疾病控制率）达到客观缓解。阿特珠单抗组和化疗组的中位无进展生存期分别为 1.4 个月（95%CI：1.2-1.5）和 4.3 个月（95%CI：1.5-5.9）。两组总生存无显著差异。阿特珠单抗组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：0.84，95%CI：0.45-1.58；p=0.60）。2 例阿特珠单抗患者（4.2%）出现 3 级疲劳，另有 2 例出现 1 级甲状腺功能减退。在 53 例可评估标本中，仅 1 例（2%）免疫组化 PD-L1 染色阳性（SP142 克隆）。
结论
阿特珠单抗单药治疗复发性 SCLC 未能显示出显著疗效。未观察到预期的安全性问题。
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