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...

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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
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Summary: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.
ISSN:2041-1723