The US Food and Drug Administration has granted regulatory approval for the use of nivolumab—an immune checkpoint inhibitor (ICI)—in the first-line treatment of advanced gastric or esophageal adenocarcinoma (GEAC), regardless of programmed death-ligand 1 (PD-L1) expression. However, the efficacy of ICIs in low PD-L1–expressing tumors remains unclear.

This study aims to reconstruct unreported Kaplan-Meier (KM) plots of PD-L1 combined positive score (CPS) subgroups of randomized phase III trials comparing the addition of ICIs with conventional chemotherapy in the first-line treatment of GEAC. A graphical reconstructive algorithm was adopted to estimate time-to-event outcomes from reported overall survival and progression-free survival (OS and PFS) KM plots describing overall or subgroup cohorts. Using reconstructed time-to-event outcomes, KMSubtraction conducts bipartite matching of patients from the reported subgroup among the overall cohort. By excluding matched patients, KM plots and survival analyses of the unreported subgroups were retrieved.

CheckMate-649, KEYNOTE-062, and KEYNOTE-590 were included. Two PD-L1 subgroups were identified with data unreported in the primary manuscripts: PD-L1 CPS 1-4 from CheckMate-649 and PD-L1 CPS 1-9 from KEYNOTE-062. No significant differences in OS and PFS were demonstrated in ICI-chemotherapy combinations when compared with chemotherapy among CheckMate-649 PD-L1 CPS 1-4 (OS: hazard ratio [HR] = 0.950, 95% CI, 0.747 to 1.209, P = .678; PFS: HR = 0.958, 95% CI, 0.743 to 1.236, P = .743) and KEYNOTE-062 PD-L1 CPS 1-9 subgroups. In the KEYNOTE-062 PD-L1 CPS 1-9 subgroup, patients treated with pembrolizumab had an increased hazard of tumor progression (HR = 2.092, 95% CI, 1.661 to 2.635, P < .001).

Using KMSubtraction, data of PD-L1 subgroups previously unreported by primary manuscripts of pivotal clinical trials were retrieved. These data suggest the lack of benefit in the addition of ICI to chemotherapy in low PD-L1–expressing GEAC tumors.

美国食品药品监督管理局（Food and Drug Administration）已批准使用 nivolumab（一种免疫检查点抑制剂 (ICI)）作为晚期胃或食管腺癌 (GEAC) 的一线治疗，无论程序性死亡配体 1 (PD- L1) 表达。然而，ICIs 在低 PD-L1 表达肿瘤中的疗效仍不清楚。

本研究旨在重建随机 III 期试验的 PD-L1 联合阳性评分 (CPS) 亚组未报告的 Kaplan-Meier (KM) 图，比较在 GEAC 的一线治疗中添加 ICI 与常规化疗。采用图形重建算法从报告的总生存期和无进展生存期（OS 和 PFS）KM 图估计总体或亚组队列的事件发生时间结果。使用重建的事件发生时间结果，KMSubtraction 对整个队列中报告的亚组中的患者进行双向匹配。通过排除匹配的患者，检索了未报告的亚组的 KM 图和生存分析。

包括 CheckMate-649、KEYNOTE-062 和 KEYNOTE-590。使用原始手稿中未报告的数据确定了两个 PD-L1 亚组：来自 CheckMate-649 的 PD-L1 CPS 1-4 和来自 KEYNOTE-062 的 PD-L1 CPS 1-9。与 CheckMate-649 PD-L1 CPS 1-4 中的化疗相比，ICI 化疗组合的 OS 和 PFS 没有显着差异（OS：风险比 [HR] = 0.950，95% CI，0.747 至 1.209，P = .678；PFS：HR = 0.958，95% CI，0.743 至 1.236，P = .743）和 KEYNOTE-062 PD-L1 CPS 1-9 亚组。在 KEYNOTE-062 PD-L1 CPS 1-9 亚组中，接受派姆单抗治疗的患者肿瘤进展风险增加（HR = 2.092, 95% CI, 1.661 to 2.635, P < .001）。

使用 KMSubtraction，检索了以前未在关键临床试验的原始手稿中报告的 PD-L1 亚组数据。这些数据表明，在低表达 PD-L1 的 GEAC 肿瘤中，将 ICI 添加到化疗中缺乏益处。