MATTERHORN Spotlight—Shaping the Treatment Horizon for Gastric/Gastroesophageal Junction (GEJ) Cancers - Episode 6
Checkpoint Inhibitors In GC/GEJC: Trials Across the Landscape
Panelists discuss how other immunotherapy trials in the perioperative setting, including studies with pembrolizumab and atezolizumab, have shown mixed results, with improved pathologic responses not necessarily translating to survival benefits. They note the negative results from the adjuvant CheckMate 577 trial.
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The landscape of checkpoint inhibitor trials in gastric cancers (GC) and gastroesophageal cancers (GEJC) reveals mixed results across different study designs and patient populations. The KEYNOTE-585 trial with pembrolizumab showed improved pathologic complete response rates but failed to demonstrate a survival benefit, likely due to differences in study design and chemotherapy backbone compared with MATTERHORN. Most patients in KEYNOTE-585 received doublet chemotherapy (FOLFOX) rather than the triplet FLOT regimen, and the overall study population and design differed significantly from MATTERHORN. These results emphasize the importance of avoiding cross-trial comparisons and highlight how study design, patient selection, and treatment backbones can significantly influence outcomes with immunotherapy combinations.
Additional trials in the perioperative space include studies with atezolizumab, another anti–PD-1 antibody, which have shown improved pathologic complete response rates with survival data pending. These represent the 3 most mature studies in the perioperative immunotherapy space for GC and GEJC. The evolution of targeted therapies and novel immunotherapy combinations in the metastatic setting provides a pipeline of potential future treatments that could eventually move into the curative perioperative space if they prove effective in advanced disease, following the established paradigm of therapeutic development.
The disappointing results from CheckMate 577, an adjuvant trial using nivolumab after preoperative chemoradiation in esophageal cancers, provide important context for understanding immunotherapy’s role across different treatment paradigms. This trial, which used the now less favored chemoradiation approach followed by surgery, failed to meet its overall survival end point despite some encouraging median survival differences. The trial included adenocarcinomas and squamous cell carcinomas with different response patterns, and the statistical significance threshold was not met despite potentially meaningful clinical differences. These results underscore the importance of treatment sequencing and patient selection in optimizing immunotherapy benefits.
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