卡瑞利珠单抗联合阿帕替尼在既往接受过治疗的携带或基因变异的晚期非小细胞肺癌患者中的疗效和安全性。
Efficacy and safety of camrelizumab plus apatinib in previously treated patients with advanced non-small cell lung cancer harboring or genetic aberration.
作者信息
Gao Guanghui, Ni Jian, Wang Yina, Ren Shengxiang, Liu Zhihua, Chen Gongyan, Gu Kangsheng, Zang Aimin, Zhao Jun, Guo Renhua, He Jianxing, Lin Xiaoyan, Pan Yueyin, Ma Zhiyong, Wang Zhehai, Fan Min, Liu Yunpeng, Cang Shundong, Yang Xinfeng, Li Weixia, Wang Quanren, Zhou Caicun
机构信息
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
Department of Oncology, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
出版信息
Transl Lung Cancer Res. 2022 Jun;11(6):964-974. doi: 10.21037/tlcr-22-22.
BACKGROUND
Camrelizumab plus apatinib shows encouraging antitumor activity and acceptable toxicity in chemotherapy-pretreated patients with advanced non-small cell lung cancer (NSCLC); however, clinical benefits from this combination regimen in NSCLC patients with EGFR mutations or ALK rearrangements (EGFR+/ALK+) have not been reported. We assessed the efficacy and safety of this combined regimen in pretreated patients with advanced NSCLC and defined EGFR/ALK status (EGFR+/ALK+) in a phase 1b/2 trial.
METHODS
Previously treated patients with advanced EGFR+/ALK+ NSCLC were enrolled and given camrelizumab 200 mg intravenously every 2 weeks plus apatinib at the recommended dose of 250 mg orally once daily. Patients harboring sensitive EGFR mutations or ALK fusion genes had received at least one EGFR/ALK TKI and a platinum-based chemotherapy regimen before the enrollment. The primary endpoint was objective response rate (ORR).
RESULTS
All 43 enrolled patients comprised the efficacy and safety analysis population. The confirmed ORR was 18.6% (95% CI: 8.4-33.4%) and the clinical benefit response rate was 27.9% (95% CI: 15.3-43.7%). Median progression-free survival (PFS) was 2.8 months (95% CI: 1.9-5.5 months) and median overall survival was not reached (95% CI: 7.3 months-not reached), with a median follow-up period of 15.7 months (range, 0.5-24.4 months). The most common grade ≥3 treatment-related adverse events (TRAEs) were hypertension (16.3%), proteinuria (11.6%) and palmar-plantar erythrodysaesthesia syndrome (9.3%). No unexpected adverse events were recorded.
CONCLUSIONS
Camrelizumab plus apatinib showed moderate antitumor activity and acceptable safety profile in previously treated patients with advanced NSCLC and EGFR or ALK genetic aberrations, which warranted further validation.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03083041. Registered March 17, 2017.
背景
卡瑞利珠单抗联合阿帕替尼在经化疗的晚期非小细胞肺癌（NSCLC）患者中显示出令人鼓舞的抗肿瘤活性和可接受的毒性；然而，该联合方案在伴有表皮生长因子受体（EGFR）突变或间变性淋巴瘤激酶（ALK）重排（EGFR+/ALK+）的NSCLC患者中的临床获益尚未见报道。我们在一项1b/2期试验中评估了该联合方案在经治晚期NSCLC患者中的疗效和安全性，并明确了EGFR/ALK状态（EGFR+/ALK+）。
方法
纳入既往接受过治疗的晚期EGFR+/ALK+ NSCLC患者，给予卡瑞利珠单抗200 mg静脉注射，每2周1次，联合阿帕替尼，推荐剂量为250 mg口服，每日1次。携带敏感EGFR突变或ALK融合基因的患者在入组前至少接受过一种EGFR/ALK酪氨酸激酶抑制剂（TKI）和铂类化疗方案。主要终点为客观缓解率（ORR）。
结果
所有43例入组患者构成疗效和安全性分析人群。确认的ORR为18.6%（95%CI：8.4-33.4%），临床获益缓解率为27.9%（95%CI：15.3-43.7%）。中位无进展生存期（PFS）为2.8个月（95%CI：1.9-5.5个月），中位总生存期未达到（95%CI：7.3个月-未达到），中位随访期为15.7个月（范围0.5-24.4个月）。最常见的≥3级治疗相关不良事件（TRAEs）为高血压（16.3%）、蛋白尿（11.6%）和手足皮肤反应综合征（9.3%）。未记录到意外不良事件。
结论
卡瑞利珠单抗联合阿帕替尼在既往接受过治疗的晚期NSCLC且伴有EGFR或ALK基因异常的患者中显示出适度的抗肿瘤活性和可接受的安全性，值得进一步验证。
试验注册
ClinicalTrials.gov标识符：NCT03083041。于2017年3月17日注册。
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