For the treatment of gastric and esophageal cancers, several pivotal trials—especially those evaluating immune checkpoint inhibitors (ICIs)—have altered the treatment landscape and led to changes in the NCCN Guidelines. In addition to pembrolizumab and nivolumab, new treatment options include trastuzumab-deruxtecan (T-DXd), ramucirumab, and trifluridine/tipiracil. These agents convey varying degrees of benefit depending on treatment line, PD-L1 expression, HER2 expression, and tumor histology. Recently, ICIs have been incorporated into the first-line treatment of HER2-negative advanced esophageal, gastroesophageal junction (GEJ), and gastric cancers, in addition to second-line treatment of advanced esophageal and GEJ cancer of squamous histology. T-DXd is another new second-line option for HER2-positive esophageal, GEJ, and gastric adenocarcinomas. ICIs are now moving into the adjuvant setting as well, and a new recommendation is nivolumab use after preoperative chemoradiation and surgery in patients who have residual disease identified at the time of their R0 resections.
Disclosures: Dr. Denlinger has disclosed serving as a scientific advisor for BeiGene, Bristol Myers Squibb Company, Exelixis Inc., Merck & Co., Inc., and Zymeworks Inc.; and receiving honoraria from Eli Lilly and Company and Taiho Pharmaceuticals Co., Ltd. Dr. Matkowskyj has disclosed receiving consulting fees from Elephas Bio and McDowell & Morrissette Professional Association. Dr. Mulcahy has disclosed no relevant financial relationships.