Anlotinib plus toripalimab as a first-line treatment in patients with advanced gastric cancer and performance status 2: the phase II APICAL-GC trial

Abstract Evidence-guided regimens for advanced gastric cancer (AGC) in patients with performance status 2 (PS 2) are limited. Here, we proposed a structured therapeutic framework termed “performance status-matched strategy”, and further conducted the APICAL-GC trial (NCT04278222). This open-label, s...

Full description

Saved in:
Bibliographic Details
Main Authors: Ke Liu, Bao-Dong Qin, Shi-Qi Chen, Xue Zhong, Xiao-Peng Duan, Ying Wu, Zhan Wang, Yan Ling, Li Sun, Chen-Yang Ye, Dong-Min Shi, Ning Gao, Xiao-Dong Jiao, Yuan-Sheng Zang
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60317-z
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850242867951304704
author Ke Liu
Bao-Dong Qin
Shi-Qi Chen
Xue Zhong
Xiao-Peng Duan
Ying Wu
Zhan Wang
Yan Ling
Li Sun
Chen-Yang Ye
Dong-Min Shi
Ning Gao
Xiao-Dong Jiao
Yuan-Sheng Zang
author_facet Ke Liu
Bao-Dong Qin
Shi-Qi Chen
Xue Zhong
Xiao-Peng Duan
Ying Wu
Zhan Wang
Yan Ling
Li Sun
Chen-Yang Ye
Dong-Min Shi
Ning Gao
Xiao-Dong Jiao
Yuan-Sheng Zang
author_sort Ke Liu
collection DOAJ
description Abstract Evidence-guided regimens for advanced gastric cancer (AGC) in patients with performance status 2 (PS 2) are limited. Here, we proposed a structured therapeutic framework termed “performance status-matched strategy”, and further conducted the APICAL-GC trial (NCT04278222). This open-label, single-arm phase II study evaluated the efficacy and safety of anlotinib combined with toripalimab among 24 treatment-naïve AGC patients with PS 2. The primary outcome was the objective response rate (ORR), with secondary endpoints including disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety profile. This trial met its prespecified endpoints, demonstrating an ORR of 58.3% (95%CI 36.6–77.9) with a DoR of 12.1 months (range: 1.43–48.5), and a DCR of 95.8% (95%CI 78.9–99.9). Median PFS reached 7.33 months (95%CI 3.83–17.1), while median OS was 15.9 months (95%CI 7.73–23.2). Treatment-related adverse events (TRAEs) of any grade occurred in 21 patients (87.5%), with grade-3 TRAEs observed in 7 patients (29.2%). No grade-4/5 TRAEs were reported. These findings provide a rationale for anlotinib plus toripalimab as a promising chemotherapy-free option for the first-line treatment of AGC patients with PS 2 under the performance status-matched strategy, showing comparable anticancer activity and a lower occurrence rate of TRAEs.
format Article
id doaj-art-2048febe34834d928f8879d4c193871b
institution OA Journals
issn 2041-1723
language English
publishDate 2025-05-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-2048febe34834d928f8879d4c193871b2025-08-20T02:00:09ZengNature PortfolioNature Communications2041-17232025-05-0116111010.1038/s41467-025-60317-zAnlotinib plus toripalimab as a first-line treatment in patients with advanced gastric cancer and performance status 2: the phase II APICAL-GC trialKe Liu0Bao-Dong Qin1Shi-Qi Chen2Xue Zhong3Xiao-Peng Duan4Ying Wu5Zhan Wang6Yan Ling7Li Sun8Chen-Yang Ye9Dong-Min Shi10Ning Gao11Xiao-Dong Jiao12Yuan-Sheng Zang13Department of Medical Oncology, Changzheng Hospital, Naval Medical UniversityDepartment of Medical Oncology, Changzheng Hospital, Naval Medical UniversityDepartment of Medical Oncology, Changzheng Hospital, Naval Medical UniversityDepartment of Medical Oncology, Changzheng Hospital, Naval Medical UniversityDepartment of Medical Oncology, Changzheng Hospital, Naval Medical UniversityDepartment of Medical Oncology, Changzheng Hospital, Naval Medical UniversityDepartment of Medical Oncology, Changzheng Hospital, Naval Medical UniversityDepartment of Medical Oncology, Changzheng Hospital, Naval Medical UniversityDepartment of Medical Oncology, Changzheng Hospital, Naval Medical UniversityDepartment of Medical Oncology, Changzheng Hospital, Naval Medical UniversityDepartment of Medical Oncology, Changzheng Hospital, Naval Medical University3D Medicines IncDepartment of Medical Oncology, Changzheng Hospital, Naval Medical UniversityDepartment of Medical Oncology, Changzheng Hospital, Naval Medical UniversityAbstract Evidence-guided regimens for advanced gastric cancer (AGC) in patients with performance status 2 (PS 2) are limited. Here, we proposed a structured therapeutic framework termed “performance status-matched strategy”, and further conducted the APICAL-GC trial (NCT04278222). This open-label, single-arm phase II study evaluated the efficacy and safety of anlotinib combined with toripalimab among 24 treatment-naïve AGC patients with PS 2. The primary outcome was the objective response rate (ORR), with secondary endpoints including disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety profile. This trial met its prespecified endpoints, demonstrating an ORR of 58.3% (95%CI 36.6–77.9) with a DoR of 12.1 months (range: 1.43–48.5), and a DCR of 95.8% (95%CI 78.9–99.9). Median PFS reached 7.33 months (95%CI 3.83–17.1), while median OS was 15.9 months (95%CI 7.73–23.2). Treatment-related adverse events (TRAEs) of any grade occurred in 21 patients (87.5%), with grade-3 TRAEs observed in 7 patients (29.2%). No grade-4/5 TRAEs were reported. These findings provide a rationale for anlotinib plus toripalimab as a promising chemotherapy-free option for the first-line treatment of AGC patients with PS 2 under the performance status-matched strategy, showing comparable anticancer activity and a lower occurrence rate of TRAEs.https://doi.org/10.1038/s41467-025-60317-z
spellingShingle Ke Liu
Bao-Dong Qin
Shi-Qi Chen
Xue Zhong
Xiao-Peng Duan
Ying Wu
Zhan Wang
Yan Ling
Li Sun
Chen-Yang Ye
Dong-Min Shi
Ning Gao
Xiao-Dong Jiao
Yuan-Sheng Zang
Anlotinib plus toripalimab as a first-line treatment in patients with advanced gastric cancer and performance status 2: the phase II APICAL-GC trial
Nature Communications
title Anlotinib plus toripalimab as a first-line treatment in patients with advanced gastric cancer and performance status 2: the phase II APICAL-GC trial
title_full Anlotinib plus toripalimab as a first-line treatment in patients with advanced gastric cancer and performance status 2: the phase II APICAL-GC trial
title_fullStr Anlotinib plus toripalimab as a first-line treatment in patients with advanced gastric cancer and performance status 2: the phase II APICAL-GC trial
title_full_unstemmed Anlotinib plus toripalimab as a first-line treatment in patients with advanced gastric cancer and performance status 2: the phase II APICAL-GC trial
title_short Anlotinib plus toripalimab as a first-line treatment in patients with advanced gastric cancer and performance status 2: the phase II APICAL-GC trial
title_sort anlotinib plus toripalimab as a first line treatment in patients with advanced gastric cancer and performance status 2 the phase ii apical gc trial
url https://doi.org/10.1038/s41467-025-60317-z
work_keys_str_mv AT keliu anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT baodongqin anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT shiqichen anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT xuezhong anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT xiaopengduan anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT yingwu anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT zhanwang anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT yanling anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT lisun anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT chenyangye anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT dongminshi anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT ninggao anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT xiaodongjiao anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial
AT yuanshengzang anlotinibplustoripalimabasafirstlinetreatmentinpatientswithadvancedgastriccancerandperformancestatus2thephaseiiapicalgctrial