安罗替尼联合派安普利单抗作为小细胞肺癌二线治疗的疗效和安全性：一项多中心、开放标签、单臂II期试验

Efficacy and safety of anlotinib plus penpulimab as second-line treatment for small cell lung cancer: A multicenter, open-label, single-arm phase II trial.

作者信息

Zhang Changgong, Chen Jianhua, Wu Huijuan, Wang Jun, Gao Liying, Zhao Jun, Sun Yan, Jia Zhongyao, Mu Xinlin, Bai Chunmei, Wang Rui, Wu Kailiang, Liu Qiang, Shi Yuankai

机构信息

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.

Department I of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410083, China.

出版信息

Cancer Pathog Ther. 2024 Feb 7;2(4):268-275. doi: 10.1016/j.cpt.2024.02.001. eCollection 2024 Oct.

BACKGROUND

Currently, the need for new therapeutic strategies involving programmed cell death protein-1 (PD-1) monoclonal antibodies in the second-line setting of small cell lung cancer (SCLC) is urgent. This study aimed to evaluate the efficacy and safety of anlotinib plus penpulimab as a second-line treatment for patients with SCLC who progressed after first-line platinum-based chemotherapy.

METHODS

This study included the patients from Cohort 4 of a single-arm, open-label, multicenter, phase II clinical trial. A safety run-in phase was performed under anlotinib (10/12 mg [QD], days 1-14) plus penpulimab (200 mg intravenously [IV], day 1) in a 21-day cycle, followed by the formal trial in which the patients received anlotinib (12 mg QD, days 1-14) plus penpulimab (200 mg IV, day 1) in a 21-day cycle. The primary endpoint of the safety run-in phase was safety. The primary endpoint of the formal trial phase was the objective response rate (ORR).

RESULTS

From April 28, 2020, to November 24, 2020, 21 patients were enrolled from 11 hospitals, including 2 in the safety run-in phase and 19 in the formal trial phase. In the formal trial phase, the ORR was 42.1% (8/19; 95% confidence interval [CI]: 17.7-66.6%). The median progression-free survival was 4.8 months (95% CI: 2.9-11.3 months), and the median overall survival was 13.0 months (95% CI: 4.6-not applicable [NA] months). The incidence of ≥grade 3 treatment-related adverse events (TRAEs) was 52.4% (11/21), and the incidence of treatment-related serious adverse events (AEs) was 28.6% (6/21). Two AE-related deaths occurred. The most common AEs were hypertension (57.1%, 12/21), hypothyroidism (42.9%, 9/21), and hypertriglyceridemia (38.1%, 8/21).

CONCLUSIONS

In patients with SCLC who progressed after first-line platinum-based chemotherapy, the second-line anlotinib plus penpulimab treatment demonstrates promising anti-cancer activity and a manageable safety profile, which warrants further investigation.

TRIAL REGISTRATION

No. NCT04203719, https://clinicaltrials.gov/.

背景

目前，在小细胞肺癌（SCLC）二线治疗中，迫切需要涉及程序性细胞死亡蛋白1（PD-1）单克隆抗体的新治疗策略。本研究旨在评估安罗替尼联合派安普利单抗作为一线铂类化疗后进展的SCLC患者二线治疗的疗效和安全性。

方法

本研究纳入了一项单臂、开放标签、多中心II期临床试验队列4的患者。在21天周期内，先进行安罗替尼（10/12mg[每日一次]，第1 - 14天）联合派安普利单抗（200mg静脉注射[IV]，第1天）的安全性导入期，随后进行正式试验，患者在21天周期内接受安罗替尼（12mg每日一次，第1 - 14天）联合派安普利单抗（200mg IV，第1天）治疗。安全性导入期的主要终点是安全性。正式试验阶段的主要终点是客观缓解率（ORR）。

结果

2020年4月28日至2020年11月24日，从11家医院招募了21例患者，其中2例在安全性导入期，19例在正式试验阶段。在正式试验阶段，ORR为42.1%（8/19；95%置信区间[CI]：17.7 - 66.6%）。中位无进展生存期为4.8个月（95% CI：2.9 - 11.3个月），中位总生存期为13.0个月（95% CI：4.6 -不可用[NA]个月）。≥3级治疗相关不良事件（TRAEs）的发生率为52.4%（11/21），治疗相关严重不良事件（AEs）的发生率为28.6%（6/21）。发生了2例与AE相关的死亡。最常见的AE是高血压（57.1%，12/21）、甲状腺功能减退（42.9%，9/21）和高甘油三酯血症（38.1%，8/21）。