Immune checkpoint inhibitors in advanced gastroesophageal adenocarcinoma: a series of patient-level meta-analyses in different programmed death-ligand 1 subgroups
Alberto Giovanni Leone, Antonello Mai, Khi Yung Fong, Dominic Wei Ting Yap, Ken Kato, E.C. Smyth, Markus Moehler, Jeremy Tey, Raghav Sundar, Joseph J. Zhao, Filippo Pietrantonio
Abstract
BACKGROUND: GEAC, we conducted an analysis leveraging individual patient data (IPD) extracted from Kaplan-Meier (KM) plots of pivotal trials. METHODS: tumors. RESULTS: 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. CONCLUSIONS: 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.