EACR26-0917

Comparative efficacy of HER2-targeted therapies in previously treated HER2-positive gastric cancer: a network meta-analysis

O. Menyhart^1,2,3, J. Fekete^1,2,3, B. Győrffy^1,2,3

¹Semmelweis University, Department of Bioinformatics, Budapest, Hungary
²HUN-REN Research Centre for Natural Sciences, Institute of Molecular Life Sciences, Budapest, Hungary
³University of Pécs, Medical School, Institute of Transdisciplinary Discoveries, Pécs, Hungary

Introduction:

In recent years, several HER2-targeted agents have been investigated in patients with previously treated HER2-positive gastric cancer. However, there has been limited direct comparison between these therapies, and their relative efficacy remains unclear.

Material and method:

Randomized controlled trials evaluating HER2-targeted therapies and chemotherapy in previously treated HER2-positive gastric (including gastroesophageal junction) cancer were identified. The network included antibody–drug conjugates, other HER2-targeted therapies, and chemotherapy-based regimens. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were extracted. A frequentist network meta-analysis was performed using a random effects model with restricted maximum likelihood estimation (REML), using the NetMetaEasy module of metaanalysisonline.com.

Result and discussion:

Eight randomized controlled trials were included. Compared with chemotherapy, anbenitamab combined with chemotherapy improved overall survival (HR 0.29, 95% CI 0.17–0.50) and progression-free survival (HR 0.25, 95% CI 0.17–0.38). Trastuzumab deruxtecan likewise improved overall survival (HR 0.59, 95% CI 0.39–0.89) and progression-free survival (HR 0.47, 95% CI 0.31–0.71). In contrast, trastuzumab emtansine, trastuzumab continuation, and lapatinib-based therapy did not show improved survival compared with chemotherapy. Ramucirumab plus paclitaxel and irinotecan did not show a statistically significant survival benefit compared with chemotherapy.

Conclusion:

This network meta-analysis suggests that recent HER2-targeted therapies, including trastuzumab deruxtecan and anbenitamab, may improve survival in previously treated HER2-positive gastric cancer. These findings may help support treatment selection in this setting.

Acknowledgement:

This project was supported by the National Research, Development, and Innovation Office (2025-1.2.1-HU-RIZONT-2025-00011 and 2024-1.2.2-ERA_NET-2024-00015) and by the Semmelweis Lendület Programme.