Effect of human epidermal growth factor receptor 2 overexpression in metastatic colorectal cancer on standard chemotherapy outcomes

Background: In metastatic colorectal cancer (mCRC), the prognostic relevance of the human epidermal growth factor receptor-2 (HER2) remains controversial. We evaluated the impact of HER2 overexpression on outcomes of standard chemotherapy in patients with mCRC. Methods: This retrospective study included patients with mCRC who received standard chemotherapy for mCRC and were tested for HER2 expression at Samsung Medical Center, Seoul, Korea, between January 15, 2017, and February 05, 2022. The HER2 test was performed using immunohistochemistry. We assessed the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) according to HER2 status. All statistical analyses were performed using SPSS (R) version 25 (IBM SPSS, Armonk, NY, USA). Results: In total, 108 patients were included; 10 (9.3%) had HER2-positive tumors. The ORR for patients with mCRC receiving standard chemotherapy did not differ for HER2-positive and HER2-negative tumors. The median PFS for patients with mCRC with HER2-positive or HER2-negative tumors after receiving first-line chemotherapy was 18.52 months [95% confidence interval (CI): 4.355-32.695] or 10.95 months (95% CI: 9.317-12.585; P=0.417), respectively, and that after second-line chemotherapy was 7.08 months (95% CI: 6.801-7.363) or 5.34 months (95% CI: 4.433-6.255; P=0.837), respectively. Likewise, OS did not differ according to HER2 expression (median OS: HER2-positive tumors, 49.1 months (95% CI: 0.000- 98.365); HER2-negative tumors, 37.7 months (95% CI: 27.111-48.366); P=0.410). Conclusions: The tumor response and survival of patients with mCRC after standard chemotherapy did not differ by HER2 expression. These findings suggest that the status of HER2 expression need not be considered when choosing regimens as the current first- and second-line treatments.