esophageal cancer
gastric cancer
comparative effectiveness research
outcome assessment
antineoplastic agents
immunotherapy
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Application of Value Framework to Phase III Trials of Immune Checkpoint Inhibitors in Esophageal and Gastric Cancer
Summary
- Immunotherapy checkpoint inhibitors are FDA-approved for first-line metastatic esophageal and gastric cancer, but not all scenarios benefit from non-selective chemo-immunotherapy application.
- ASCO Net Health scores were consistently higher in esophageal cancer trials compared to gastric cancer trials, with differences noted in high vs. low PD-L1 expression and squamous vs. adenocarcinoma histology.
- KEYNOTE 181 trial showed marginal net health scores for adenocarcinoma and CPS<10.
- KEYNOTE-059 trial initially showed promise but subsequent trials failed, leading to withdrawal of single-agent pembrolizumab approval in 2021.
- Avelumab and nivolumab had mixed results; biomarkers like PD-L1 and tumor mutation burden should be used in trials to exclude unresponsive patients.
- There is a concern that more people are eligible for immunotherapy than those who actually benefit, leading to increased costs without proportional benefits.
- Pembrolizumab is FDA-approved for HER2+ esophageal and gastric adenocarcinoma based on KEYNOTE 811 trial results.
- CHECKMATE 648 showed promising overall survival benefits for nivolumab and ipilimumab in squamous esophageal cancer.
- Triplet cytotoxic chemotherapy (DOF, FLOT, FOLFIRINOX) may be helpful for patients with low PD-L1 unlikely to respond to immunotherapy.
- Study limitations include difficulty in separating GE junction cancers, endpoint representation issues, score variability, and heterogenous populations.
- This is the first study using ASCO and ESMO value assessments across immunotherapy trials for esophageal and gastric cancer, highlighting differences and informing clinical guidelines.
Advanced and metastatic esophageal and gastric cancer portends poor prognosis with limited durable treatment options. In 2020, GLOBOCAN estimated approximately 544 076 deaths globally from esophageal cancer, which is one of every 18 cancer-related deaths, and 768 793 deaths from stomach cancer, which is one of every 13 cancer-related deaths. Gastric cancer has the fourth highest number of cancer-related deaths after lung, colorectal, and liver cancers.
While survival has improved over the past several decades, esophageal and gastric cancers still have poor survival outcomes of less than 20% at 5 years...
esophageal cancer, gastric cancer, comparative effectiveness research, outcome assessment, antineoplastic agents, immunotherapy
