Comparative efficacy of CLDN18.2-directed regimens in advanced gastric/gastroesophageal junction adenocarcinoma: a meta-analysis of single-arm trials.

OBJECTIVE

To compare the efficacy and safety of different Claudin (CLDN)18.2-directed regimens in advanced gastric/gastroesophageal junction adenocarcinoma.

METHODS

PubMed, Web of Science, CNKI, and Wanfang databases were searched up to June 2026. Single-arm trials evaluating CLDN18.2-targeted gastric/gastroesophageal junction adenocarcinoma therapies were included. Meta-analysis was performed to pool objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and safety outcomes.

RESULTS

Ten studies (710 patients) were included. The pooled mPFS was 4.19 months (95% CI 2.90-5.49), the pooled ORR was 30.3% (95% CI 14.8%-48.1%), and the pooled DCR was 78.5% (95% CI 61.2%-92.1%). Subgroup analyses by treatment type revealed substantial efficacy differences. Zolbetuximab monotherapy showed limited activity (mPFS 1.84 months, ORR 4.8%, DCR 37.9%), which improved markedly when combined with chemotherapy (mPFS 6.61 months, ORR 63.7%, DCR 95.6%). Antibody-drug conjugates (ADCs) achieved notable efficacy in pretreated patients (mPFS 5.31 months, ORR 36.7%, DCR 84.3%). Chimeric antigen receptor T-cell (CAR-T) therapy demonstrated substantial anti-tumor activity (mPFS 5.80 months, ORR 54.2%, DCR 96.1%), but the evidence was based on a single study and should be considered preliminary.

CONCLUSION

Zolbetuximab plus chemotherapy is the preferred strategy for patients eligible for chemotherapy. ADCs represent a viable option for patients with chemotherapy resistance or intolerance. Zolbetuximab monotherapy has limited efficacy and should be used sparingly. CAR-T showed promising activity but remains investigational.