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Background We aimed to investigate response and prognostic factors in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic colorectal cancer (mCRC) and compare the curative effect on patients who received different therapy regimens (including chemotherapy and chemotherapy combined with targeted drugs). Methods We retrospectively analyzed all HER2 positive mCRC patients treated at Peking University Cancer Hospital between September 2011 and February 2021. We divided 63 HER2 positive mCRC into group A and group B according to the use of trastuzumab or not. Besides, we assigned four subgroups according to the first-line therapies of  KRAS/NRAS/BRAF  WT patients. The Kaplan–Meier estimator was used to calculate PFS and OS. Univariable analysis and Cox proportional hazards models were used to analyze the association between clinicopathological features and survival outcomes. Results Among 63 patients, 54 (85.7%) were  KRAS/NRAS/BRAF  wild-type (WT). Univariate analysis showed that the male sex, primary lesions in the right colon, simultaneous metastasis, and unresectable primary lesions were significant risk factors for poor survival of HER2 positive mCRC ( P  &lt; 0.05). Using Cox proportional hazards models, we found that the two factors of gender and resection of primary lesions were independent prognostic factors  (P &lt;  0.05). The median PFS and median OS of HER2-positive patients with mCRC who received first-line treatment were 8.4 months [95% confidence interval (CI): 5.0–11.7] and 48.2 months (95% CI: 23.5–72.8), respectively. The log-rank test revealed a significant difference in median OS survival between group A and group B (χ 2  = 5.852,  P  = 0.016), and the two groups were divided according to the use or absence of trastuzumab treatment. In  KRAS/NRAS/BRAF  WT patients, there was a significant difference in median PFS and median OS between the fourth group patients (chemotherapy plus trastuzumab) and each of the other three groups ( P  &lt; 0.05). Conclusions The two factors of gender and resection for primary lesion may be independent prognostic factors of advanced HER2 positive colorectal cancer patients. For patients with HER2-positive mCRC, patients in the chemotherapy combined with trastuzumab group have better efficacy than those without trastuzumab.

Clinicopathological features of HER2 positive metastatic colorectal cancer and survival analysis of anti-HER2 treatment