曾接受免疫检查点抑制剂治疗的晚期非小细胞肺癌患者使用卡博替尼加阿特珠单抗还是单用卡博替尼？COSMIC-021 1b 期研究结果

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports Pub Date : 2024-03-20 DOI:10.1016/j.jtocrr.2024.100666

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引用次数: 0

摘要

导言我们评估了卡博替尼加阿特珠单抗或卡博替尼单药治疗既往接受过免疫检查点抑制剂（ICI）治疗的晚期NSCLC的疗效和安全性。方法COSMIC-021（NCT03170960）是一项晚期实体瘤的1b期多中心研究。这项分析纳入了既往接受过一种 ICI 且既往接受过少于或等于两种全身抗癌疗法的 IV 期非鳞状 NSCLC 患者，这些患者的 EGFR、ALK、ROS1 或 BRAF-V600E 基因组无可操作性畸变。患者每天口服卡博替尼40毫克，每三周静脉注射atezolizumab 1200毫克（联合用药组）或每天口服卡博替尼60毫克（单药卡博替尼组）。联合用药队列的主要终点是研究者根据实体瘤反应评价标准 v1.1 确定的客观反应率。结果 81例接受联合治疗的患者和31例接受单药卡博替尼治疗的患者接受了大于或等于一个剂量的研究治疗。随访中位数（范围）分别为26.1个月（12.1-44.2）和22.4个月（1.5-29.0）。联合用药队列的客观应答率为20%（95%置信区间：11.7%-30.1%），单药卡博替尼队列的客观应答率为6%（95%置信区间：0.8%-21.4%）。联合用药队列中有86%的患者发生了治疗相关不良事件（TRAEs），单药卡博替尼队列中有90%的患者发生了治疗相关不良事件（TRAEs）；3/4级TRAEs发生率分别为44%和48%。有两例5级TRAE：肺炎（1例，联合用药）和胃溃疡出血（1例，单药）。肿瘤细胞中的 PD-L1 表达和肿瘤突变负荷均与疗效无关。结论卡博赞替尼联合阿特珠单抗治疗既往 ICI 治疗进展后的晚期 NSCLC 表现出适度的临床活性和可控的毒性。

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Cabozantinib Plus Atezolizumab or Cabozantinib Alone in Patients With Advanced NSCLC Previously Treated With an Immune Checkpoint Inhibitor: Results From the Phase 1b COSMIC-021 Study

Introduction

We evaluated efficacy and safety of cabozantinib plus atezolizumab or cabozantinib alone in advanced NSCLC previously treated with an immune checkpoint inhibitor (ICI).

Methods

COSMIC-021 (NCT03170960) is a phase 1b, multicenter study in advanced solid tumors. This analysis included patients with stage IV non-squamous NSCLC without actionable genomic aberrations in EGFR, ALK, ROS1, or BRAF-V600E who progressed on one prior ICI and less than or equal to two prior lines of systemic anticancer therapy. Patients received cabozantinib 40 mg orally/day plus atezolizumab 1200 mg intravenously every three weeks (combination cohort) or cabozantinib 60 mg orally/day (single-agent cabozantinib cohort). Primary end point of the combination cohort was objective response rate per Response Evaluation Criteria in Solid Tumors v1.1 by investigator. Outcomes in the single-agent cabozantinib cohort were exploratory.

Results

Eighty-one patients assigned to combination therapy and 31 assigned to single-agent cabozantinib received greater than or equal to one dose of study treatment. Median (range) follow-up was 26.1 months (12.1–44.2) and 22.4 months (1.5–29.0), respectively. Objective response rate was 20% (95% confidence interval: 11.7%–30.1%) in combination cohort and 6% (95% confidence interval: 0.8%–21.4%) in single-agent cabozantinib cohort. Treatment-related adverse events (TRAEs) occurred in 86% of patients in the combination cohort and 90% in the single-agent cabozantinib cohort; grade 3/4 TRAEs were 44% and 48%, respectively. There were two grade 5 TRAEs: pneumonitis (n = 1, combination) and gastric ulcer hemorrhage (n = 1, single-agent). Neither PD-L1 expression in tumor cells nor tumor mutation burden correlated with outcomes.