Adding zolbetuximab to chemotherapy improves survival outcomes in patients with unresectable or metastatic gastric/gastroesophageal junction cancer, according to phase 3 results presented at the ASCO Plenary Series March 2023 session.
Both progression-free survival (PFS) and overall survival (OS) were improved in patients who received the combination therapy, compared with patients who received chemotherapy alone, said study presenter Manish A. Shah, MD, of Weill Cornell Medicine in New York, New York.
In this phase 3 trial (GLOW, ClinicalTrials.gov Identifier: NCT03653507), 507 patients were randomly assigned to receive either zolbetuximab plus standard-of-care capecitabine-oxaliplatin (CAPOX; n=254) or placebo plus CAPOX (n=253).
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Patients had previously untreated, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma that was CLDN18.2-positive and HER2-negative, with an ECOG performance status of 0 or 1. Baseline characteristics were balanced between the arms.
The primary endpoint was PFS. The median PFS was 8.21 months with zolbetuximab-CAPOX and 6.80 months with CAPOX-placebo (hazard ratio [HR], 0.687; 95% CI, 0.544-0.866; P =.0007).
“The difference in progression-free survival increased with time,” Dr Shah noted.
At 12 months, the PFS rate was 35% in the zolbetuximab arm and 19% in the placebo arm. At 24 months, the PFS rate in the zolbetuximab arm was double that of the placebo arm, at 14% vs 7%, respectively.
The median OS was 14.39 months in the zolbetuximab arm and 12.16 months in the placebo arm (HR, 0.771; 95% CI, 0.615-0.965; P =.0118). The 12-month OS rate was 58% and 51%, respectively. The 24-month OS rates were 29% and 17%, respectively.
Rates of treatment-emergent adverse events (TEAEs) were similar between the arms. Any-grade TEAEs occurred in 98.8% of patients in the zolbetuximab arm and 98.0% of those in the placebo arm. The rate of grade 3 or higher TEAEs was 72.8% and 69.9%, respectively.
The most common TEAEs in the zolbetuximab arm were nausea (68.5%) and vomiting (66.1%). The rate of TEAEs leading to treatment discontinuation was 7.4% in the zolbetuximab arm and 4.4% in the placebo arm. There were 6 fatal TEAEs in the zolbetuximab arm and 7 in the placebo arm.
“Zolbetuximab successfully targets CLDN18.2 and meets a truly unmet medical need in the treatment of metastatic gastric/GE [gastroesophageal] junction adenocarcinoma,” Dr Shah concluded. “GLOW confirmed that zolbetuximab plus chemotherapy is a new standard-of-care treatment for patients with CLDN18.2-positive, HER2-negative locally advanced, unresectable or metastatic gastric and GE junction adenocarcinoma.”
Disclosures: This research was supported by Astellas Pharma Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Xu R-H, Shitara K, Ajani JA, et al. Zolbetuximab + CAPOX in 1L claudin-18.2+ (CLDN18.2+)/HER2− locally advanced (LA) or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Primary phase 3 results from GLOW. ASCO Plenary Series. March 22, 2023. Abstract 405736.
