Dr Janjigian on Future Research Directions for Immunotherapy in Gastric/GEJ/Esophageal Cancer

"For all immune checkpoint blockade, we need to bring it to [patients with] earlier-stage [disease]. I’m excited and hopeful that we will do so very shortly with [the read] out of some of our data in a perioperative setting with a FLOT-based combination plus anti–PD-L1 durvalumab in the MATTERHORN study, and of course, combination therapies in the first line setting.”

Yelena Y. Janjigian, MD, the chief of the Gastrointestinal Oncology Service at the Memorial Sloan Kettering Cancer Center, discussed future research directions regarding immune checkpoint inhibitor–based therapies for the treatment of patients with gastric, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma.

A push for immune checkpoint blockade in patients with earlier-stage disease and combination therapies in the first-line setting are 2 future directions in research that could be coming soon, Janjigian began. She noted that a FLOT (docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil)-based combination with anti–PD-L1 agent durvalumab (Imfinzi) evaluated in patients with resectable gastric/GEJ cancer in the phase 3 MATTERHORN study (NCT04592913) could be an example of a step forward.

However, the phase 3 LEAP-015 trial (NCT04662710), which evaluated pembrolizumab (Keytruda) plus lenvatinib (Lenvima) in patients with previously untreated, locally advanced, unresectable or metastatic, HER2-negative gastroesophageal adenocarcinoma, did not meet its other primary end point of overall survival (OS), according to data from the final analysis, she explained. Janjigian pondered if there is a more optimal subpopulation that would benefit from this immune checkpoint blockage approach. In HER2-positive disease, she explained that the combination of trastuzumab (Herceptin), immunotherapy, and chemotherapy is suitable in the first-line setting.

Ongoing research in focusing on refining combination approaches in the first-line setting, bringing immunotherapy to the perioperative setting, and exploring novel approaches for second- and later-line treatments for patients who have experienced disease progression after receiving immunotherapy, she said. For example, she explained that treatment based on the phase 3 CheckMate649 trial (NCT02872116) may not work for every patient, and additional treatment options are needed beyond the frontline setting, such as off-the-shelf natural killer T-cell therapies and next-generation CTLA-4 inhibitors, she concluded.