1. Low Programmed Death-Ligand 1–Expressing Subgroup Outcomes of First-Line Immune Checkpoint Inhibitors in Gastric or Esophageal Adenocarcinoma
- Author
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Yiong Huak Chan, Joseph J. Zhao, Elizabeth C Smyth, Nicholas Syn, Chong Boon Teo, Yu Yang Soon, Dominic Wei Ting Yap, Raghav Sundar, and Benjamin Kye Jyn Tan
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Esophageal Neoplasms ,medicine.medical_treatment ,Immune checkpoint inhibitors ,Esophageal adenocarcinoma ,Pembrolizumab ,Adenocarcinoma ,B7-H1 Antigen ,Stomach Neoplasms ,Internal medicine ,medicine ,Humans ,Immune Checkpoint Inhibitors ,Randomized Controlled Trials as Topic ,Chemotherapy ,business.industry ,Hazard ratio ,Progression-Free Survival ,Clinical trial ,Clinical Trials, Phase III as Topic ,Tumor progression ,Cohort ,Disease Progression ,business - Abstract
PURPOSE 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. MATERIALS AND METHODS 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. RESULTS 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). CONCLUSION 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.
- Published
- 2022