Treatment Patterns and Prognostic Factors of Anti-HER2 Therapy in HER2-positive Advanced/Recurrent Gastric Cancer.

Human epidermal growth factor receptor 2 (HER2) over-expression occurs in approximately 10-20% of gastric cancers. While HER2-positive tumors tend to behave more aggressively, anti-HER2 therapy has markedly improved outcomes in this subgroup. Trastuzumab (Tmab) and trastuzumab deruxtecan (T-DXd) are key agents, yet real-world data on how these treatments are delivered and tolerated remain scarce.

We retrospectively reviewed 43 patients with advanced or recurrent HER2-positive gastric or gastroesophageal junction cancer who received chemotherapy between 2014 and 2025. Clinical features, laboratory data, and treatment courses were extracted from medical records. Overall survival (OS) was analyzed using Kaplan-Meier methods and prognostic factors using Cox regression.

The median age was 70 years, and 81% of tumors were HER2 immunohistochemistry (IHC) 3+. Median OS was 29.6 months, with 3- and 5-year survival rates of 36% and 29%, respectively. Longer OS was linked with HER2 3+ status, gastrectomy, single metastatic site, normal lactate dehydrogenase (LDH), low neutrophil-to-lymphocyte ratio, and lower modified Glasgow Prognostic Score (mGPS). Patients maintaining anti-HER2 therapy ≥260 days lived significantly longer than those treated for a shorter duration (p<0.001). On multivariate analysis, elevated LDH, mGPS=2, and short anti-HER2 exposure independently predicted poorer survival.

Sustained anti-HER2 therapy was strongly associated with longer survival. Adjusting the cytotoxic partner to manage toxicity may help patients continue trastuzumab-based treatment and achieve better outcomes.
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Authors

Wada Wada, Kurokawa Kurokawa, Takahashi Takahashi, Saito Saito, Hagi Hagi, Nakai Nakai, Momose Momose, Yamashita Yamashita, Tanaka Tanaka, Makino Makino, Eguchi Eguchi, Doki Doki, Satoh Satoh
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