A multicenter retrospective study on the clinical features of patients with human epidermal growth factor receptor 2-positive colorectal cancer (HGCSG2304).

BACKGROUND: In metastatic colorectal cancer (mCRC), human epidermal growth factor receptor 2 (HER2)-positive disease is a molecular subtype for targeted therapy; however, real-world data remain limited. METHODS: A multicenter retrospective study of patients with HER2-positive mCRC diagnosed between 2010 and 2023 at 14 institutions in Japan was conducted. In patients with RAS wild-type tumors, outcomes were compared based on the molecular targeted agent (anti-epidermal growth factor receptor [EGFR] antibody or bevacizumab) combined with first-line chemotherapy. In patients treated with trastuzumab plus pertuzumab (Tmab+Per), outcomes and safety, with infusion-related reactions (IRRs) assessed. RESULTS: Forty-five patients were included. In patients with RAS wild-type tumors, outcomes were comparable between the anti-EGFR antibody (n = 17) and bevacizumab (n = 9) groups (progression-free survival: 15.6 vs. 12.0 months; hazard ratio: 0.94, 95% confidence interval: 0.38-2.35, overall survival: 38.4 vs. 32.0 months; hazard ratio: 0.91, 95% confidence interval: 0.30-2.74, p = 0.87). Twenty patients received Tmab+Per, with a median progression-free survival of 3.1 months and an objective response rate of 10%. Greater benefit was observed in patients with RAS wild-type and HER2 immunohistochemistry 3+ tumors (objective response rate 28.6%). IRRs occurred in 14.2% of patients receiving prophylactic antihistamines and 41.7% of those who did not (p = 0.35). CONCLUSIONS: In patients with HER2-positive mCRC, first-line treatment efficacy appeared comparable between the anti-EGFR antibody and bevacizumab groups. Tmab+Per demonstrated modest activity, with greater benefit observed in patients with RAS wild-type and HER2 immunohistochemistry 3+ tumors. Appropriate patient selection and IRR management remain important.