POTLIGHT, GLOW trials lead to FDA approval of zotuximab for chemotherapy of gastric/GEJ cancer

The SPOTLIGHT and GLOW clinical trials have resulted in the U.S. Food and Drug Administration (FDA)approval of the Zolbetuximab-Vyloy combination with chemotherapy as first-line treatment for patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma with CLDN18.2-positive tumors. The two double-blind, multicenter trials evaluated the primary efficacy outcome of progression-free survival (PFS), and the additional outcome measure of overall survival (OS).

A total of565 patients participated in the SPOTLIGHT trial and were randomized in a 1:1 ratio to receive zotuximab plus mFOLFOX6 chemotherapy or placebo plus mFOLFOX6 chemotherapy. The median PFS of the zotuximab/chemotherapy group and the placebo/chemotherapy group were 10.6 months (95%CI: 8.9-12.5) and 8.7 months (95%CI: 8.2-10.3) respectively (HR=0.751; [95%CI: 0.598-0.942 ]; P=0.0066), while the median OS was 18.2 months (95%CI: 16.4-22.9) and 15.5 months (95%CI: 13.5-16.5) (HR=0.750; [95%CI: 6.01-0.936]; P=0.0053).

In theGLOW trial, a total of 507 patients were enrolled and randomized in a 1:1 ratio to receive zotuximab combined with CAPOX chemotherapy or placebo combined with CAPOX chemotherapy. Median PFS was 8.2 months (95% CI: 7.5-8.8) in the zotuximab/chemotherapy group and 6.8 months (95% CI: 6.1-8.1) in the placebo/chemotherapy group (HR=0.687; [95% CI: 0.544-0.866]; P=0.0007). The median OS were 14.4 months (95%CI: 12.3-16.5) and 12.2 months (95%CI: 10.3-13.7) respectively (HR=0.771; [95%CI: 0.615-0.965]; P=0.0118).

Inthe SPOTLIGHT trial, the most common serious adverse reactions (occurring in ≥2% of patients) included vomiting, nausea, neutropenia, diarrhea, ileus, and pyrexia. In the GLOW trial, these reactions included vomiting, nausea, decreased appetite, thrombocytopenia, upper gastrointestinal bleeding, and diarrhea.

Based on these trials, the currently recommended dose of zotuximab for fluoropyrimidine- and platinum-containing chemotherapy regimens is the first intravenous dose800 mg/m2, followed by 600 mg/m2 intravenously every 3 weeks, or 400 mg/m2 intravenously every 2 weeks.

References:https://www.docwirenews.com/post/spotlight-glow-trials-lead-to-fda-approval-of-zolbetuximab-clzb-with-chemotherapy-for-gastric-gej-cancer