Although immune checkpoint inhibitors are not yet approved for first-line therapy in these populations, the new research could lead to a new standard of care.
Although immunotherapy would be a major shift in treatments for gastric and esophageal cancers, 3 studies have found benefits for these patient populations, who currently have poor survival rates. Results of these studies were presented during the ESMO Virtual Congress 2020.
The first trial, CheckMate 649, evaluated nivolumab plus chemotherapy versus chemotherapy alone as first-line treatment in patients with nonhuman epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer, gastro-esophageal junction cancer, or esophageal cancer. All participants had adenocarcinoma histology.
According to the study results, nivolumab combined with chemotherapy improved overall survival and progression-free survival in patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) tumors of 5 or greater. The investigators also observed improvements in patients with PD-L1 CPS tumors of 1 or greater, and in the overall patient population.
“The results are clinically very relevant,” said Salah-Eddin Al-Batran, MD, director of the Institute of Clinical Cancer Research, in a statement. “Based on this trial, for patients with HER2-negative gastric adenocarcinoma, esophageal adenocarcinoma, or gastro-esophageal junctional adenocarcinoma with PD-L1 CPS ³5 tumors, the addition of nivolumab to chemotherapy will become the standard of care for first-line treatment.”
The ATTRACTION 4 trial also investigated non-HER-2-positive advanced gastric cancer, gastro-esophageal junction cancer, and esophageal cancer, but it was performed only in Asian patients and the primary endpoints were designed for all-comers rather than a specific CPS value. The trial found that first-line treatment with nivolumab plus chemotherapy improved the co-primary progression-free survival endpoint, but not overall survival.
“The improvement in progression-free survival was clinically relevant, and the trial strongly supports the results of CheckMate 649,” Al-Batran said. “Overall survival was not improved, possibly because all-comers were treated or because patients in Asia receive more subsequent therapies than Western populations.”
Finally, the KEYNOTE 590 trial evaluated first-line chemotherapy with or without pembrolizumab in patients with squamous cell carcinoma of the esophagus, adenocarcinoma of the esophagus, or Siewert type 1 gastro-esophageal junction adenocarcinoma. The trial found that pembrolizumab plus chemotherapy improved overall survival in patients with squamous cell carcinoma of the esophagus with PD-L1 CPS ³10 tumors, all squamous cell carcinomas, all patients with CPS ³10 tumors, and the overall study population.
Most participants with esophageal cancer had squamous cell carcinoma (73%) and those with adenocarcinoma were a small subgroup. The results among this subgroup were an experimental analysis, but they found benefits in overall survival and progression-free survival consistent with the benefits in the overall patient population.
“The results of these trials offer oncologists new treatment options,” Al-Batran concluded. “In the first-line setting, there is a clear change of our standard of care, in which patients with high PD-L1 expression will be candidates for immune checkpoint inhibitors plus chemotherapy. However, more data are needed on the subgroups who benefit from the treatment.”
Immunotherapy Is Beneficial In Gastric and Oesophageal Cancers, Studies Show [news release]. Lugano, Switzerland; September 21, 2020: European Society for Medical Oncology. Accessed September 23, 2020. https://www.esmo.org/meetings/esmo-virtual-congress-2020/meeting-resources/news/esmo2020-gastric-oesophageal-cancer-immunotherapy-checkmate649-attraction4-keynote590.