Efficacy and safety of first-line sintilimab plus anlotinib versus chemotherapy for metastatic non-small cell lung cancer: a phase II, open-label, randomized controlled trial

IF 20.1 1区医学 Q1 ONCOLOGY

Cancer Communications Pub Date : 2025-01-10 DOI:10.1002/cac2.12654

Tianqing Chu, Hua Zhong, Zhuang Yu, Jing Wang, Yanqiu Zhao, Xiaoqian Mu, Xinmin Yu, Xun Shi, Qingming Shi, Maojing Guan, Cuimin Ding, Nan Geng, Jialin Qian, Baohui Han

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Abstract

Background

The prognosis for non-small cell lung cancer (NSCLC) patients treated with standard platinum-based chemotherapy was suboptimal, with safety concerns. Following encouraging results from a preliminary phase I study, this phase II trial investigated the efficacy and safety of first-line sintilimab and anlotinib in metastatic NSCLC.

Methods

In this open-label, randomized controlled trial (NCT04124731), metastatic NSCLC without epithelial growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or proto-oncogene tyrosine-protein kinase ROS (ROS1) mutations, and previous treatments for metastatic disease were enrolled. Participants were randomly assigned in a 1:1 ratio to either sintilimab (200 mg every 3 weeks) plus anlotinib (12 mg D1-14 every 3 weeks) or a standard platinum-based chemotherapy regimen. Patients in the chemotherapy group were permitted to switch to sintilimab after disease progression. The primary endpoint was the objective response rate (ORR).

Results

From November 2019 to March 2023, 99 patients were randomized into the sintilimab plus anlotinib group (n = 49) and the chemotherapy group (n = 50). The ORR was significantly higher in the sintilimab plus anlotinib group (44.9%; 95% confidence interval [CI] = 30.7%-59.8%) compared to the chemotherapy group (18.0%; 95% CI = 8.6%-31.4%, P = 0.003). Progression-free survival (PFS) was also notably longer (median: 14.4 vs. 5.6 months; hazard ratio [HR] = 0.39; 95% CI = 0.23-0.67; P < 0.001). The 24-month overall survival rate was 58.4% (95% CI = 40.4%-72.6%) and 43.2% (95% CI = 26.0%-59.2%), respectively. The rate of grade 3 or higher treatment-related adverse events was lower in the sintilimab plus anlotinib group (28.0%) than in the chemotherapy group (49.0%), especially for the hematological toxicities.

Conclusion

First-line sintilimab plus anlotinib showed improved ORR and PFS, alongside a superior safety profile, compared to the standard platinum-based chemotherapy for metastatic NSCLC patients.

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一线辛替单抗加anlotinib与化疗治疗转移性非小细胞肺癌的疗效和安全性：一项开放标签随机对照试验

背景：非小细胞肺癌（NSCLC）患者接受标准铂基化疗的预后不理想，存在安全性问题。在初步I期研究取得令人鼓舞的结果之后，这项II期试验调查了一线sintilimab和anlotinib治疗转移性NSCLC的有效性和安全性。方法：在这项开放标签、随机对照试验（NCT04124731）中，纳入了无上皮生长因子受体（EGFR）、间变性淋巴瘤激酶（ALK）或原癌基因酪氨酸蛋白激酶ROS （ROS1）突变的转移性NSCLC，以及既往治疗过的转移性疾病。参与者以1:1的比例随机分配到辛替单抗（每3周200毫克）加安洛替尼（每3周12毫克D1-14）或标准铂基化疗方案。化疗组的患者在疾病进展后被允许改用辛替单抗。主要终点为客观缓解率（ORR）。结果：2019年11月至2023年3月，99例患者随机分为辛替单抗联合安洛替尼组（n = 49）和化疗组（n = 50）。辛替单抗联合安洛替尼组的ORR显著更高(44.9%；95%可信区间[CI] = 30.7%-59.8%)与化疗组(18.0%；95% ci = 8.6% ~ 31.4%, p = 0.003)。无进展生存期（PFS）也明显更长(中位数：14.4个月vs. 5.6个月；风险比[HR] = 0.39；95% ci = 0.23-0.67；P < 0.001)。24个月总生存率分别为58.4% （95% CI = 40.4% ~ 72.6%）和43.2% （95% CI = 26.0% ~ 59.2%）。辛替单抗加安洛替尼组3级及以上治疗相关不良事件发生率（28.0%）低于化疗组（49.0%），特别是血液毒性。结论：与转移性NSCLC患者的标准铂基化疗相比，一线sintilimab + anlotinib显示出改善的ORR和PFS，以及优越的安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Communications Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

25.50

自引率

4.30%

发文量

153

审稿时长

4 weeks

期刊介绍： Cancer Communications is an open access, peer-reviewed online journal that encompasses basic, clinical, and translational cancer research. The journal welcomes submissions concerning clinical trials, epidemiology, molecular and cellular biology, and genetics.