This past year, the COVID-19 pandemic continued to impact the practice of medicine and the dissemination of clinical research findings presented in scientific forums. Organizations such as the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology presented virtual meetings that delivered information on cutting-edge research and advances in cancer treatment and management.
Virtual formats present several challenges in reaching intended audiences that the Year in Review series attempts to ameliorate by presenting effective and timely information on oncology treatment advances to clinicians engaged in cancer delivery and research.
This edition of Year in Review is focused on gastric cancer, esophageal cancer, and gastroesophageal junction (GEJ) cancer, and immunotherapy and targeted therapies used in the management of these cancers. In 2021, the US Food and Drug Administration approved nivolumab for the treatment of resected esophageal or GEJ cancer and advanced esophageal squamous-cell carcinoma; pembrolizumab for the treatment of HER2-positive gastric cancer, esophageal, or GEJ carcinoma; and trastuzumab deruxtecan for the treatment of HER2-positive gastric adenocarcinomas. These approvals, which were based on key clinical trial results, offer expanded treatment options for patients.
The CheckMate-649 study found that nivolumab in combination with fluoropyrimidine- and platinum-containing chemotherapy for advanced or metastatic gastric cancer, GEJ cancer, and esophageal adenocarcinoma demonstrated statistically significant improvement in progression-free survival and overall survival in patients with PD-L1 combined positive score ≥5 and a statistically significant overall survival improvement for all randomized study patients. In patients with GEJ or esophageal cancer, the CheckMate-577 clinical trial found nivolumab adjuvant therapy increased disease-free survival over placebo. The CheckMate-032 trial yielded promising efficacy and safety results in patients with gastroesophageal cancer treated with nivolumab and nivolumab plus ipilimutmab therapy. The 3-year ATTRACTION-2 follow-up study confirmed the efficacy of nivolumab in patients with previously treated advanced gastric/GEJ cancer.
DKN-01 in combination with tislelizumab ± chemotherapy as first-line or second-line therapy demonstrated promising response rates and safety data in patients with advanced DKK1-high gastroesophageal adenocarcinoma in the phase 2a DisTinGuish Part A trial. Ramucirumab and irinotecan combination therapy in patients with advanced gastric cancer yielded promising antitumor activity and safety results in a single-arm phase 2 clinical study. In the GAMMA-1 clinical trial, andecaliximab plus oxaliplatin, leucovorin, and 5-fluorouracil (modified [m] FOLFOX6) use in patients with metastatic gastric adenocarcinoma improved efficacy in elderly patients.
The phase 3 KEYNOTE-811 clinical trial found that pembrolizumab and trastuzumab plus first-line standard of care improved responses in patients with HER2-positive advanced gastric or GEJ cancer. Likewise, the KEYNOTE-181 study demonstrated improved overall survival in patients with advanced esophageal cancer treated with second-line pembrolizumab when compared with chemotherapy.
The phase 1b/2 PANTHERA study showed triplet pembrolizumab, trastuzumab, and chemotherapy as first-line therapy in patients with HER2-positive advanced gastric/GEJ cancer demonstrated promising efficacy for this patient group. Patients with HER2-positive gastric or GEJ cancer treated with second-line trastuzumab deruxtecan demonstrated promising responses in the phase 2 DESTINY-Gastric02 trial.
First-line treatment of camrelizumab with chemotherapy was found to improve survival in patients with advanced or metastatic esophageal squamous-cell carcinoma in the ESCORT-1st phase 3 clinical trial. Treatment-naïve patients with FGFR2b-positive, HER2-negative advanced gastric cancer treated with bemarituzumab and mFOLFOX6 had statistically meaningful improvement in progression-free survival, overall survival, and overall response rate in the phase 2 FIGHT clinical trial.
In addition to the presentation and publication of these clinical trial results, 2021 also saw the release of ASCO clinical guidelines for the treatment of patients with advanced esophageal cancer.
It is our pleasure to present the highlights of these clinical findings and more in this issue of Year in Review.
Joseph Chao, MD
Department of Medical Oncology & Therapeutics Research
GI Medical Oncology Section
City of Hope Comprehensive Cancer Center