HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer

Figure 1 Assessment of intratumoral HER2 heterogeneity. Assessment of intratumoral HER2 heterogeneity was conducted from at least two different portions of the same tumor, and more than three biopsy specimens were obtained from each portion. Homogeneity was defined by all assessed portions showing HER2 positivity, and heterogeneity was defined as a tumor with any portions that did not show HER2 positivity. HER2: Human epidermal growth factor receptor 2.

Figure 2 Patient flow chart. HER2 positivity was observed in 127 (16.3%) of 776 patients with metastatic or unresectable adenocarcinoma. After exclusion of 39 patients for the listed reasons, HER2 homogeneity was observed in 65 (Homo group) and HER2 heterogeneity was observed in 23 (Hetero group). HER2: Human epidermal growth factor receptor 2.

Figure 3 Clinical response for patients with or without intratumoral human epidermal growth factor receptor 2 heterogeneity. Tumor shrinkage (left) and clinical response (right) was evaluated by RECIST ver. 1.1 for 58 patients who have measurable metastatic lesions. ORR was 79.5% in the Homo group, which was significantly higher than that in the Hetero group (35.7%, P = 0.002). CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; ORR: Overall response rate (CR plus PR).

Figure 4 OS and PFS with or without intratumoral human epidermal growth factor receptor 2 heterogeneity. Kaplan-Meier curves of OS (left) and PFS (right) in both groups was shown with the median follow-up of 18.5 mo (range, 4.7-88.0 mo). MST and median PST in the Hetero group were significantly worse than those in the Homo group. MST: Median survival time; HR: Hazard ratio; CI: Confidence interval; OS: Overall survival; PFS: Progression-free survival.

Figure 5 Overall survival by HER2 score and intratumoral HER2 heterogeneity. MST for the Homo group with HER2 3+ was longest (28.2 mo), followed by Hetero group with 3+ (14.6 mo), Homo group with 2+ (12.9 mo) and Hetero group with 2+ (7.2 mo). MST: Median survival time; HR: Hazard ratio; CI: Confidence interval; HER2: Human epidermal growth factor receptor 2.