ASCO Expert Perspective
“The combination of PD-1 inhibitor plus chemotherapy is standard of care for first line treatment of gastroesophageal cancers. We are in need of new tools in the toolkit for patients with advanced gastroesophageal cancer. The addition of domvanalimab has promising efficacy but also does not appear to add side effects to current standard treatments." – Pamela Kunz, MD, ASCO Expert in Gastrointestinal Cancers
The addition of the T-cell immunoglobulin and ITM domain (TIGIT) inhibitor domvanalimab to the programmed cell death protein 1 (PD-1) inhibitor zimberelimab and chemotherapy may improve outcomes for patients with advanced gastroesophageal cancer. These results will be presented during the November 2023 session of the American Society of Clinical Oncology (ASCO) Plenary Series.
The addition of PD-1 inhibitors to front-line chemotherapy transformed the field and became standard of care for patients in metastatic gastroesophageal cancer. However, resistance to this treatment often develops, presenting a need for additional treatment options.
In this arm of the EDGE-Gastric study, researchers enrolled 41 patients with previously untreated gastric, gastroesophageal junction, or esophageal adenocarcinoma. The median time patients spent taking the treatment was 33 weeks, 59% of patients continued on to protocol therapy as outlined in the study, and there were no adverse event related deaths. The intent-to-treat objective response rate – or the number of patients who saw improvement – for all patients on the study was 59% and the progression-free survival at 6 months was 77%.
PD-1 is a protein expressed on immune cells. PD-1 interacts with another protein called PD-L1. PD-L1 helps cancer cells avoid the immune system, allowing them to grow. By blocking this interaction between the PD-1 and PD-L1 proteins, it boosts the body’s immune system and the ability to fight cancer. In patients who had a tumor area positivity score for PD-L1 of ≥5%, the objective response rate was 80% and the 6-month progression-free survival rate was 93%.
Serious treatment-related side effects occurred in 24% of patients, with none related to domvanalimab and zimberelimab.
“Preliminary results of this study are encouraging, particularly in patients whose tumors have high expression of PD-L1. However, additional follow up will allow for the evaluation of longer-term efficacy measures, such as progression-free survival and overall survival. Importantly, the safety profile of this new combination is similar to that of anti-PD-1 plus chemotherapy,” said lead study author Yelena Y. Janjigian, MD, Chief, Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center.
Disclosures for Dr. Kunz: coi.asco.org/share/TLS-NHXP/Kunz%2c%20Pamela
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