虽然免疫检查点抑制剂 (ICI) 在程序性死亡配体 1 高 (PD-L1high) 晚期胃食管腺癌 (GEAC) 中的疗效已得到充分证实，但其在 PD-L1low GEAC 中的疗效仍存在重大争议。为了阐明 ICI 在 PD-L1low 和 PD-L1阴性 GEAC 中的益处，我们利用从关键试验的 Kaplan-Meier (KM) 图提取的个体患者数据 (IPD) 进行了分析。随机临床试验的 KM 曲线调查了 ICI 的疗效高级 GEAC 的 ICI 摘自已发表的文章。 IPD 是从报告的曲线中提取的，对于未报告的 KM 图，KMSubtraction 用于检索生存数据。对 PD-L1low 肿瘤进行了患者水平的荟萃分析。在人表皮生长因子受体 2 (HER2) 阴性的情况下，汇总了来自 KEYNOTE-859 的 PD-L1 组合阳性评分 (CPS) 1-4 亚组 KM 图、CHECKMATE-649 和 RATIONALE-305 在添加抗程序性细胞死亡蛋白 1（抗 PD-1）药物后显示出适度的总生存 (OS) 益处 [风险比 (HR) 0.868，P = 0.018] 。同样，我们对 KEYNOTE-859、KEYNOTE-062 和 RATIONALE-305 中的 PD-L1 CPS 1-9 亚组进行的 IPD 荟萃分析显示了适度的 OS 获益（HR 0.840，P = 0.002。）相反，当 CPS 5将 KEYNOTE-859 和 RATIONALE-305 的 -9 亚组 KM 图合并在一起，在 ICI 化疗组中未发现显着的 OS 获益（HR 0.867，P = 0.181），尽管该亚组相对较小。在 PD-L1low HER 中-2 负 GEAC，一线 ICI 的好处虽然不大，但很显着。需要进一步的转化工作，以更好地选择在这种情况下可以从免疫治疗中受益的患者。同时，必须考虑替代治疗方案，例如用于治疗 Claudin18.2 阳性疾病的 zolbetuximab。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

While the benefit of immune checkpoint inhibitors (ICI) is well established in programmed death-ligand 1 high (PD-L1high) advanced gastroesophageal adenocarcinoma (GEAC), there remains significant controversy about their benefit in PD-L1low GEAC. To elucidate the benefit of ICI in PD-L1low and PD-L1negative GEAC, we conducted an analysis leveraging individual patient data (IPD) extracted from Kaplan-Meier (KM) plots of pivotal trials.KM curves from randomized clinical trials investigating the efficacy of ICI for advanced GEAC were extracted from published articles. IPD were extracted from the reported curves, and, in the case of unreported KM plots, KMSubtraction was used to retrieve survival data. A patient-level meta-analysis was conducted for PD-L1low tumors.In the human epidermal growth factor receptor 2 (HER2)-negative setting, pooled PD-L1 combined positive score (CPS) 1-4 subgroup KM plots from KEYNOTE-859, CHECKMATE-649, and RATIONALE-305 showed a modest overall survival (OS) benefit with the addition of an anti-programmed cell death protein 1 (anti-PD-1) agent [hazard ratio (HR) 0.868, P = 0.018]. Similarly, a modest OS benefit was shown by our IPD meta-analysis of PD-L1 CPS 1-9 subgroups from KEYNOTE-859, KEYNOTE-062, and RATIONALE-305 (HR 0.840, P = 0.002.) Conversely, when CPS 5-9 subgroup KM plots from KEYNOTE-859 and RATIONALE-305 were pooled together, no significant OS benefit was found in the ICI-chemotherapy arm (HR 0.867, P = 0.181), although this subgroup was relatively small.In PD-L1low HER-2 negative GEAC, the benefit of first-line ICI is modest, yet significant. Further translational work is warranted to better select patients who could benefit from immunotherapy in this setting. Meanwhile, alternative therapeutic options such as zolbetuximab in Claudin18.2-positive disease must be taken into account.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.