Dr. Van Cutsem on Primary Findings from the SPOTLIGHT and GLOW Trials in Metastatic Gastric Cancer

Eric Van Cutsem, MD, PhD, professor of medicine, division head, Department of Digestive Oncology, University of Leuven (KUL), University Hospitals Gasthuisberg, Leuven Belgium, discusses primary efficacy and safety findings from the phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) trials investigating the monoclonal antibody zolbetuximab (IMAB362) in metastatic gastric cancer.

The international, randomized, placebo-controlled SPOTLIGHT trial compared the use of zolbetuximab plus mFOLFOX6 vs mFOLXOX6 and placebo in patients with Claudin 18.2 (CLDN18.2)–positive, HER2-negative, locally advanced, unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, Van Cutsem begins. A significant proportion of patients with advanced gastric cancer are CLDN18.2-positive, he notes.

Primary results from the study presented at the 2023 ASCO Gastrointestinal Cancers Symposium showed that zolbetuximab plus mFOLXOX6 elicited statistically and clinically significant improvements in both progression-free survival (PFS) and overall survival (OS), Van Cutsem states.

Positive topline results from the GLOW trial of zolbetuximab in combination with capecitabine and oxaliplatin (CAPOX) were also recently reported, Van Cutsem adds. This trial evaluated this regimen vs CAPOX plus placebo as first-line treatment in the same population as SPOTLIGHT, and zolbetuximab plus data demonstrated a statistically significant PFS and OS for patients treated with zolbetuximab plus CAPOX.

These randomized studies support use of zolbetuximab in combination with current chemotherapy regimens as a novel and effective treatment strategy for CLDN18.2-positive advanced gastric cancer, Van Cutsem states.

Additionally, HER2, microsatellite instability status and PD-1 biomarker testing is now standard in the frontline setting for advanced gastric cancer. If zolbetuximab receives approval in this setting, CLDN18.2 should be assessed as an additional prognostic marker in this disease space, Van Cutsem concludes.