1. Median progression-free survival in zolbetuximab group was greater than in the placebo group (10.6 months vs. 8.7 months).
2. There were significantly more serious adverse events in the Zolbetuximab group with nausea, vomiting, and decreased appetite being the most common symptoms.
Evidence Rating Level: 1 (Excellent)
Study Rundown: First-line treatment for gastric and gastro-esophageal adenocarcinoma includes chemotherapy including folinic acid, fluorouracil, and oxaliplatin regimen (FOLFOX). Zolbetuximab is a monoclonal antibody targeting claudin-18 isoform 2 (CLDN18.2) that may be used in patients with gastric cancer, although little is known about its efficacy to date. This randomized controlled trial aimed to compare the safety and efficacy of zolbetuximab in patients with CLDN18.2-positive, HER2-negative gastric or gastro-esophageal adenocarcinoma. The primary outcome was progression-free survival while key secondary outcomes included overall survival and time to confirmed deterioration. According to study results, patients in the zolbetuximab group reported greater progression-free and overall survival. There were more serious treatment-emergent adverse events in the zolbetuximab group but there was no increase in treatment-related mortality between groups. This study was strengthened by a randomized design with longitudinal follow-up, thus increasing the validity of the results.
Relevant Reading: Duration of Adjuvant Chemotherapy for Stage III Colon Cancer
In-depth [randomized-controlled trial]: Between Jun 21, 2018, and Apr 1, 2022, 2735 patients were screened for eligibility across 215 centers in 20 countries. Included were patients ≥ 18 years with CLDN18.2-positive, HER2-negative gastric or gastro-esophageal adenocarcinoma and an Eastern Cooperative Oncology Group (ECOG) score of 0 to 1. Altogether, 565 patients (283 in zolbetuximab plus mFOLFOX6 and 282 in placebo plus mFOLFOX6) were included in the final analysis. The primary outcome of progression-free survival was greater in the zolbetuximab group than placebo (10.61 months vs. 8.67 months) with a significant reduction in disease progression among zolbetuximab patients (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.60-0.94, p=0.0066). Although patients in the zolbetuximab group reported greater grade 3 or 4 adverse events than those in the placebo group (87% vs. 78%), overall survival was significantly increased in the zolbetuximab group (hazard ratio [HR] 0.75, 95% CI 0.60-0.94, p=0.0053). Findings from this study suggest that zolbetuximab may be safe and effective in patients with locally advanced unresectable or metastatic gastric or gastro-esophageal adenocarcinoma.
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