Zolbetuximab added to mFOLFOX6 improved the progression-free survival (PFS) and overall survival (OS) of patients with claudin-18.2-positive (CLDN18.2-positive)/HER2−negative, locally advanced, unresectable or metastatic, gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma, primary results of the SPOTLIGHT study revealed.

SPOTLIGHT is a global phase 3 trial randomizing newly diagnosed patients with CLDN18.2-positive/HER2-negative, locally advanced, mG/GEJ adenocarcinoma (N=565) 1:1 to mFOLFOX6 plus zolbetuximab or to mFOLFOX6 plus placebo.1 PFS was the primary endpoint of the study and Dr. Kohei Shitara (National Cancer Center Hospital East, Japan) presented the primary findings at ASCO-GI 2023.

After a median follow-up of 12.9 months, the median PFS was significantly higher if patients were treated with zolbetuximab compared with mFOLFOX6 only (10.6 months vs 8.7 months; HR 0.75; P=0.0066). The corresponding 24-month PFS rates were 24% and 15%, respectively. The OS results confirmed the benefit of the addition of zolbetuximab to mFOLFOX6 with a median OS of 18.2 months compared with 15.5 months for patients who received mFOLFOX6 only (HR, 0.75; P=0.0053).

The safety profile of zolbetuximab and mFOLFOX6 was acceptable, according to the authors. The incidence of treatment-emergent adverse events (TEAEs) was comparable for the two treatment arms, but grade 3 or higher nausea (16.1% vs 6.5%) and vomiting (16.1% vs 5.8%) were more common in the zolbetuximab arm.

Zolbetuximab plus mFOLFOX6 candidates may be a new standard-of-care therapy for patients with CLDN18.2-positive/HER2-negative, locally advanced, mG/GEJ adenocarcinoma.

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