Dr. Janjigian on Pembrolizumab Triplet in HER2+ Esophagogastric Cancer

Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the rationale behind the plasma and tumor-based biomarker analysis of pembrolizumab (Keytruda) in combination with trastuzumab (Herceptin) and chemotherapy in HER2-positive metastatic esophagogastric cancer.

Patients on the trial experienced an unprecedented overall response rate (ORR) of 91%, according to Janjigian; this compared favorably with the historical control combination of chemotherapy and trastuzumab (Herceptin), as seen in the phase 3 ToGA study. In that study, chemotherapy plus trastuzumab demonstrated a 47% ORR in HER2-positive gastric cancer, says Janjigian.

Furthermore, the combination of pembrolizumab plus trastuzumab, capecitabine, and oxaliplatin resulted in durable progression-free survival, with 70% of patients progression free at 6 months, meeting the primary end point of the trial. The median overall survival in this population was 27 months, which was very impressive, according to Janjigian. Based on these data, the phase 3 KEYNOTE-811 study is accruing patients and the goal is to confirm the robust survival benefit seen with this approach.

Results from an analysis of tissue- and blood-based biomarkers conducted as part of the phase 2 study was presented at the 2020 ASCO Virtual Scientific Program. With this analysis, investigators were trying to determine how to predict which patients will respond and have durable responses to this treatment approach. Most patients will respond, says Janjigian; 100% of patients experienced a reduction in tumor burden. Since 16% of patients in this study experienced complete responses, it's important to determine which patients can potentially achieve cure with this combination in the long term, concludes Janjigian.