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

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‐...

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Main Authors: 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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Language:English
Published: Wiley 2025-04-01
Series:Cancer Communications
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Online Access:https://doi.org/10.1002/cac2.12654
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author 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
author_facet 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
author_sort Tianqing Chu
collection DOAJ
description 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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spelling doaj-art-8fb964bc157744c4afb0e604787da60a2025-08-20T03:10:21ZengWileyCancer Communications2523-35482025-04-0145444245510.1002/cac2.12654Efficacy and safety of first‐line sintilimab plus anlotinib versus chemotherapy for metastatic non‐small cell lung cancer: a phase II, open‐label, randomized controlled trialTianqing Chu0Hua Zhong1Zhuang Yu2Jing Wang3Yanqiu Zhao4Xiaoqian Mu5Xinmin Yu6Xun Shi7Qingming Shi8Maojing Guan9Cuimin Ding10Nan Geng11Jialin Qian12Baohui Han13Department of Respiratory and Critical Care Medicine Chest Hospital Affiliated to Shanghai Jiao Tong University Shanghai P. R. ChinaDepartment of Respiratory and Critical Care Medicine Chest Hospital Affiliated to Shanghai Jiao Tong University Shanghai P. R. ChinaDepartment of Oncology the Affiliated Hospital of Qingdao University Qingdao Shandong P. R. ChinaDepartment of Oncology the Affiliated Hospital of Qingdao University Qingdao Shandong P. R. ChinaDepartment of Respiratory Medicine Henan Cancer Hospital/Affiliated Cancer Hospital of Zhengzhou University Zhengzhou Henan P. R. ChinaDepartment of Respiratory Medicine Henan Cancer Hospital/Affiliated Cancer Hospital of Zhengzhou University Zhengzhou Henan P. R. ChinaDepartment of Thoracic Oncology Cancer Hospital Affiliated to the University of Chinese Academy of Sciences Hangzhou Zhejiang P. R. ChinaDepartment of Thoracic Oncology Cancer Hospital Affiliated to the University of Chinese Academy of Sciences Hangzhou Zhejiang P. R. ChinaDepartment of Medical Oncology Anhui Chest Hospital Hefei Anhui P. R. ChinaDepartment of Medical Oncology Anhui Chest Hospital Hefei Anhui P. R. ChinaDepartment of Respiratory Medicine The Fourth Hospital of Hebei Medical University Shijiazhuang Hebei P. R. ChinaDepartment of Respiratory Medicine The Fourth Hospital of Hebei Medical University Shijiazhuang Hebei P. R. ChinaDepartment of Respiratory and Critical Care Medicine Chest Hospital Affiliated to Shanghai Jiao Tong University Shanghai P. R. ChinaDepartment of Respiratory and Critical Care Medicine Chest Hospital Affiliated to Shanghai Jiao Tong University Shanghai P. R. ChinaAbstract 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.https://doi.org/10.1002/cac2.12654non‐small cell lung cancermetastaticphase II trialsintilimabanlotinibtreatment response
spellingShingle 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
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
Cancer Communications
non‐small cell lung cancer
metastatic
phase II trial
sintilimab
anlotinib
treatment response
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic non‐small cell lung cancer
metastatic
phase II trial
sintilimab
anlotinib
treatment response
url https://doi.org/10.1002/cac2.12654
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