PD-1 Inhibitors for First-Line Treatment of Patients With Gastroesophageal Cancers

At Great Debates and Updates in Gastrointestinal Malignancies in New York, New York, Ryan Moy, MD, PhD, Columbia University Irving Medical Center, New York, New York, discussed first-line use of PD-1 inhibitors for the treatment of patients with gastroesophageal cancers. 

Transcript: 

Hi, my name is Ryan Moy, I'm a medical oncologist and assistant professor of medicine at Columbia University Irving Medical Center focusing on gastrointestinal malignancies, in particular upper GI tumors. Today I participated in a debate looking at the role of anti PD-1 or claudin-18.2 targeted therapy in first line treatment of metastatic gastroesophageal cancer.

Immunotherapy with PD-1 inhibitors has been studied in multiple global randomized phase 3 studies including CheckMate 649 and KEYNOTE-859 leading to the approval of nivolumab or pembrolizumab in combination with first-line chemotherapy. In addition to newer biomarkers claudin-18.2 is a molecule that is expressed in about 30 to 40 percent of gastroesophageal cancers and recent studies have looked at zolbetuximab, an antibody against claudin-18.2, combined with chemotherapy in 2 randomized trials SPOTlight and GLOW.

I took the side arguing that PD-1 inhibitors are the better target for first-line treatment. We have longer-term follow up data and duration of response with the addition of PD-1 inhibitors to chemotherapy as compared to zolbetuximab. There’s an improvement in overall response rate across multiple studies with PD-1 inhibitors, and in addition, PD -1 inhibitors may have better effect in more proximal gastroesophageal junction tumors. Lastly, they're important biomarker subsets such as MSI-high disease and HER2-positive disease that also benefit from PD-1 inhibitors. Finally, the toxicity profile, we have more experience with PD-1 inhibitors in terms of managing side effects with zolbetuximab. In the SPOTlight trial there was a 16% grade 3 toxicity of nausea and vomiting. 

We do think that claudin-18.2 is an important and emerging biomarker in gastroesophageal cancers and also looking forward to newer therapies as well as emerging data combining claudin-18.2with immunotherapy and chemotherapy in the Lester trial. 

Source: 

Moy R.Debate: Best targeted therapy for first-line gastroesophageal cancer: PD-1 inhibitors or claudin-18.2 (CLDN18.2)? Presented at Great Debates and Updates in Gastrointestinal Malignancies. May 17-18, 2024. New York, NY.