Deng Ning, Yan Zhijing, Wang Shengpeng, Song Menghuan, Hu Hao
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China; Centre for Pharmaceutical Regulatory Sciences, University of Macau, Macau, China.
Clin Ther. 2025 Feb;47(2):148-157. doi: 10.1016/j.clinthera.2024.11.014. Epub 2024 Dec 5.
The efficacy of several novel combinations of anti-programmed cell death protein 1 or its ligand antibodies with chemotherapy, which have become the new standard first-line combination therapy with favorable outcomes, was still not certain in patients with different combined positive score (CPS) grades. This research aimed to evaluate the efficacy of immune checkpoint inhibitor immunotherapy or immunochemotherapy at different CPS grades, compared with chemotherapy.
Kaplan-Meier (KM) curve reconstruction was employed to assess the overall survival (OS) and progression-free survival (PFS) of patients with gastric cancer. The graphical reconstruction algorithm was used to estimate the time-to-event outcomes from Kaplan-Meier curves of the overall cohort or reported subgroups (depending on CPS). KMSubtraction was used to derive the unreported survival data by matching participants in the overall cohort and known subgroups.
This analysis included 5072 patients in 5 trials (CheckMate 649, KEYNOTE-859, ORIENT-16, KEYNOTE-062, and JAVELIN Gastric 100). Immunochemotherapy exhibited more effectiveness than chemotherapy in most cases. For the overall cohort, sintilimab + chemotherapy exhibited the best effect in OS (hazard ratio [HR], 0.65; 95% CI, 0.55-0.76). Nivolumab + chemotherapy (HR, 0.75; 95% CI, 0.67-0.84), sintilimab + chemotherapy (HR, 0.52; 95% CI, 0.41-0.65), and pembrolizumab + chemotherapy (HR, 0.68; 95% CI, 0.58-0.81) exhibited favorable outcomes in OS in patients with a CPS ≥1, 5, and 10, respectively, and similarly in PFS. Avelumab + chemotherapy performed similarly to chemotherapy in OS but had poor PFS in the reported subgroup.
Finding suggests that immune checkpoint inhibitors combined with chemotherapy could enrich patients with benefits regardless of CPS grades, though subtle efficacy in low CPS subgroups. This study compared the efficacy of different immunotherapies combined with chemotherapy in patients with gastric cancer, but we acknowledge some differences between reconstructed and original data. Hopefully there will be more research investigating comparisons between current therapies rather than with chemotherapy only in the future.
几种抗程序性细胞死亡蛋白1或其配体抗体与化疗的新型联合疗法已成为具有良好疗效的新标准一线联合疗法，但其在不同联合阳性评分（CPS）分级患者中的疗效仍不明确。本研究旨在评估免疫检查点抑制剂免疫疗法或免疫化疗在不同CPS分级下与化疗相比的疗效。
采用Kaplan-Meier（KM）曲线重建来评估胃癌患者的总生存期（OS）和无进展生存期（PFS）。图形重建算法用于从整个队列或报告的亚组（取决于CPS）的Kaplan-Meier曲线估计事件发生时间结局。KMSubtraction用于通过匹配整个队列和已知亚组中的参与者来推导未报告的生存数据。
该分析纳入了5项试验（CheckMate 649、KEYNOTE-859、ORIENT-16、KEYNOTE-062和JAVELIN Gastric 100）中的5072例患者。在大多数情况下，免疫化疗比化疗表现出更高的疗效。对于整个队列，信迪利单抗+化疗在OS方面表现出最佳效果（风险比[HR]，0.65；95%置信区间，0.55-0.76）。纳武利尤单抗+化疗（HR，0.75；95%置信区间，0.67-0.84）、信迪利单抗+化疗（HR，0.52；95%置信区间，0.41-0.65）和帕博利珠单抗+化疗（HR，0.68；95%置信区间，0.58-0.81）分别在CPS≥1、5和10的患者的OS中表现出良好的结局，在PFS中情况类似。阿维鲁单抗+化疗在OS方面与化疗表现相似，但在报告的亚组中PFS较差。
研究结果表明，免疫检查点抑制剂联合化疗无论CPS分级如何都能使患者受益，尽管在低CPS亚组中的疗效不明显。本研究比较了不同免疫疗法联合化疗在胃癌患者中的疗效，但我们承认重建数据与原始数据之间存在一些差异。希望未来会有更多研究探讨当前疗法之间的比较，而不仅仅是与化疗的比较。
