Advances in the Treatment of Gastric Cancer: 2020–2021

David H. Ilson


Curr Opin Gastroenterol. 2021;37(6):615-618. 

In This Article

Abstract and Introduction


Purpose of Review: To review studies from 2020 to 2021 in esophagogastric cancer.

Recent Findings: After up front D2 gastrectomy for lymph node-positive gastric cancer, 6 months of adjuvant chemotherapy with S-1 and oxaliplatin achieved superior disease-free survival (DFS) compared with 1 year of S-1. The addition of adjuvant radiotherapy, however, added no benefit. After chemoradiotherapy and surgery in esophageal and gastroesophageal junction cancer, in patients with residual disease found at surgery, 1 year of adjuvant nivolumab substantially improved DFS compared with observation alone, leading to regulatory approval for adjuvant nivolumab. In metastatic esophagogastric cancer, the addition of either pembrolizumab or nivolumab to first-line chemotherapy improved response, disease free, and overall survival with the greatest survival benefit dependent on programmed death receptor ligand, programmed death receptor ligand -1 status, leading to regulatory approval for these agents. A preliminary report of a phase 3 trial adding pembrolizumab to first-line chemotherapy with trastuzumab in HER2-positive gastric cancer reported a significant improvement in response, leading to regulatory approval for pembrolizumab. The fibroblast growth factor receptor appears to be a promising new target in gastroesophageal cancer based on phase 2 data for bemarituzumab.

Summary: Optimal adjuvant chemotherapy after D2 resection of node-positive gastric cancer is 6 months of a fluorinated pyrimidine and oxaliplatin, with no benefit for adjuvant radiotherapy. Adjuvant nivolumab after resection of esophageal cancer after chemoradiotherapy improves DFS and is a new care standard. Pembrolizumab added to first-line chemotherapy in both HER2-positive and negative esophagogastric cancer improves outcome and is a new standard of care. Nivolumab added to first-line chemotherapy in HER2-negative gastric cancer improves treatment outcome and is a new care standard.


Collectively esophageal and gastric cancer account for over 1.3 million cases annually with a high rate of fatality. In patients with gastric cancer, a D1 surgery is defined as gastrectomy and resection of group 1 (perigastric) lymph nodes. D2 gastrectomy involves resection of group 1 and group 2 lymph nodes (i.e., lymph nodes around the left gastric artery, common hepatic artery, celiac axis, splenic artery, and proper hepatic artery). Perioperative chemotherapy with FLOT (infusional 5-fluorourical, leucovorin, oxaliplatin, and docetaxel), or adjuvant chemotherapy after D2 resection with a fluorinated pyrimidine with or without a platinum drug, improves survival. Postoperative adjuvant radiation therapy is reserved for patients undergoing less than a D1 resection. In metastatic gastric cancer, chemotherapy combines a fluorinated pyrimidine with a platinum agent, and if patients are HER2-positive trastuzumab is included. Adding a third agent (epirubicin or docetaxel) increases toxicity without clearly improving survival. Paclitaxel and ramucirumab is standard second-line chemotherapy. For third-line therapy, trifluridine tipiracil is typically used. After initial approval of immune checkpoint inhibitors for patients with chemotherapy refractory metastatic esophagogastric cancer who test programmed death receptor ligand, programmed death receptor ligand -1 (PDL-1) positive or are microsatellite instability (MSI) high, recent first-line trials discussed below now have established an earlier role for these agents.