To evaluate the efficacy and safety of zolbetuximab in combination with chemotherapy for treating advanced gastric and gastroesophageal junction adenocarcinoma.
Approach:
Clinical Trials Reviewed: The review encompasses phase I–III clinical trials, including the SPOTLIGHT, GLOW, FAST, and ILUSTRO trials.
Key Findings:
Zolbetuximab demonstrated clinical activity and tolerability in early phase studies.
The phase II FAST study showed improved progression-free survival (PFS) with a hazard ratio of 0.44 and overall survival (OS) with a hazard ratio of 0.55 when zolbetuximab was added to EOX chemotherapy.
The SPOTLIGHT study indicated a 25% reduction in death risk with zolbetuximab plus mFOLFOX6, with median OS of 18.23 months compared to 15.54 months.
The GLOW study showed a nearly 23% reduction in death risk with zolbetuximab plus CAPOX, with median OS of 14.39 months compared to 12.16 months.
Common adverse events included nausea and vomiting, primarily in the first treatment cycle.
Interpretation:
Zolbetuximab represents a significant advancement in treating advanced G/GEJ adenocarcinoma with high CLDN18.2 expression.
Limitations:
Challenges in optimizing the threshold for CLDN18.2 positivity.
Need for establishing treatment regimens for patients with concurrent CLDN18.2 and PD-L1 expression.
Conclusion:
Zolbetuximab is a novel treatment option for advanced G/GEJ adenocarcinoma with high CLDN18.2 expression.
