Do all patients with HER2-positive gastric/GEJ cancer benefit from trastuzumab?

185 Background: Trastuzumab-based chemotherapy became the standard option for patients with HER2 (+) metastatic gastric cancer after ToGA study. However, the OS benefit was not found in Asian and diffuse-type cancer patients. The aim of the current study is to analyze whether Asian ethnicity or poorly differentiated histology (PDH) affects the clinical outcomes of patients who were treated with trastuzumab-based chemotherapy. Methods: We collected the medical records of the patients with HER2 (+) (IHC3+ or IHC2+&FISH+) gastric/GEJ cancer who were treated with trastuzumab-based chemotherapy. The ORR, PFS, and OS were compared according to the patients’ clinicopathologic features and data from ToGA trial. Results: From March 2012 to June 2014, data of 163 Asian patients from 11 institutes in South Korea were collected. The median age was 60 (range 27-85) and the male:female ratio was 116 (71.2%):47 (28.8%). 157 (96.3%) had stomach cancer and 6 (3.7%) had GEJ cancer. Fourteen (8.6%), 62 (38.0%), 71 (43.6%) and 11 (6.7%) patients had well, moderately, poorly differentiated tubular adenocarcinoma (TAC) and signet ring cell carcinoma (SRC), respectively. The ORR was 52.7% (86/163) which is similar to that of the ToGA trial. (47%) The median PFS was 9.8 months (95% CI 8.6 – 11.0 and the median OS was 18.5 months. (95% CI 16.5 – 20.5) These numerical data are slightly better than those of the ToGA trial. (PFS, 6.7 months; OS, 16.0 months) Next, we investigated if PDH (poorly differentiated TAC + SRC) affected on clinical outcomes. The ORR (50.0% vs. 56.6%, p = 0.408) and the PFS (8.8 months vs. 11.2 months, p = 0.109) were slightly inferior in PDH patients but still, they were better than that of the ToGA trial. The median OS was significantly shorter for PDH patients (14.1 months vs. 19.0 months, p = 0.046). Conclusions: While subset analysis of ToGA trial has demonstrated that trastuzumab-based chemotherapy may not be beneficial for Asian ethnicity and poorly differentiated histology, our real world data suggested that even in Asian and patients with PDH, trastuzumab-based chemotherapy is associated with improved clinical outcomes in patients with HER2 (+) gastric cancer.