HER-2 overexpression in gastroesophageal junction (EGJ) adenocarcinoma as a predictor of prognosis in patients treated with perioperative chemotherapy.

Abstract

151 Background: Approximately 15% of all gastroesophageal adenocarcinomas overexpress HER-2. This is more common in intestinal subtype and proximal tumors. HER-2 status is associated with poor prognosis in non-metastatic patients, but its prognostic impact on the outcomes of pts treated with perioperative chemotherapy (CT) is unclear. Methods: The aim of this study was to retrospectively analyze the influence of HER-2 status on the overall survival (OS) and Relapse Free Survival (RFS) of pts with locally advanced gastroesophageal adenocarcinoma treated with perioperative CT. HER-2 positive tumors were defined by 3+ immunohistochemical staining or fluorescence in situ hybridization positivity. Independent variables used in the Cox model were: Lauren's subtype, clinical staging, and a combination of primary site and HER-2 status. Results: A total of 97 patients were included: median age was 62y, 62 (63.9%) were male; N = 57 (58.8%) had cT3 tumors and 60 (60.1%) had cN+. Lauren’s subtype was intestinal in N = 35 (36.1%), and diffuse in N = 44 (45.4%). CT regimens were mainly FOLFOX (46.4%), EOX (23.7%) or DCF (13.4%). Regarding primary site and HER-2 status: gastric HER-2 negative N = 61, Gastric HER-2 positive N = 8, GEJ HER-2 negative N = 23, GEJ HER-2 positive N = 5. In a Cox multivariate analyses for OS and RFS, EGJ HER-2 positive pts had higher chance of recurrence (HR = 3.57, 1.08 – 11.77, p = 0.03) and death (HR = 6.14, 1.83 – 20.60, p = 0.003). EGJ HER-2+ 3y RFS was zero and 3y OS was 20%. Conclusions: EGJ HER-2+ tumors carried a dismal prognosis and had little benefit from conventional perioperative CT strategies. Although further studies are needed to confirm our data, we believe that a different approach, possible combining anti-HER-2 drugs, should be tested in this scenario.