P-195 A cohort of patients (pt) with HER2-positive (HER2+) advanced gastroesophageal cancer (aGEC) treated at our institution after a decade of tailored targeted therapy

Abstract

aGEC is a dismal prognosis disease with limited treatment options. Molecular characterization of these tumors revealed 15-20% of HER2+ assessed either by immunohistochemistry (IHC 3+) or by fluorescence in situ hybridization (FISH amplified/IHC 2+). Since 2010, the TOGA trial established a combination of chemotherapy (CHT) plus trastuzumab (TTZ), a specific antiHER2 mAb, as the standard of care (SoC) in first line for HER2+ aGEC pt. After a decade of implementing this personalized therapy, we aim to describe the clinic-pathological characteristics and outcomes of the subset of HER2+ aGEC pt treated at our Institution. We performed a descriptive analysis of 29 pt diagnosed with HER2+ aGEC treated with CHT plus TTZ at Catalan Institute of Oncology, Badalona, from 2016 to 2021. For the purposes of this study, pt enrolled in clinical trials were excluded. Data regarding demographic and cancer characteristics, treatment and survival outcomes were collected retrospectively from available electronic medical records. Data analysis was performed using SPSS program. Median age was 61 years (29-78) and 90% of pt were men. Regarding primary location, 42% were gastroesophageal junction (GEJ), 34% gastric and 24% were distal esophagus tumors. All tumors were adenocarcinomas. HER2 status was reported as IHC 3+ in 23 pt, whilst 6 pt were IHC 2+, in which FISH resulted amplified in all cases. Metastatic disease was present in 22 pt at diagnosis, and the other 7 pt were initially staged as locally advanced disease before progressing into advanced disease. Most common metastatic sites were hepatic (18%), peritoneal (14%) or a combination of different locations (59%). Only 2 pt (9%) had single organ metastasis in a different location from the previously described (adenopathy and lung). All pt were treated with a platinum and fluoropirimidine-based CHT plus TTZ SoC. Median progression-free survival (PFS) following first line was 8.4 months (m) [(95% confidence interval (CI) 5.4-11.4]. Median overall survival (OS) was 14.63 m [95% CI 5.7-23.6]. To date, 25 pt were deceased, but one pt is still receiving CHT plus TTZ as first line. Noteworthy, 2 pt outliers who achieved complete response to CHT plus TTZ are currently under surveillance without specific cancer treatment. Second line treatment was feasible in 13 pt, 4 pt received a further third line and even 1 pt was able to receive a fourth line. The TTZ-based therapy has significantly improved the outcomes for HER2+ aGEC pt, as illustrated by OS>12m and 50% pt receiving alternative treatment beyond first line. Survival outcomes observed in our cohort were consistent with previously described outcomes available in the literature. Deeper characterization of the outliers is warranted to shed more light into the molecular determinants that predict efficacy. Furthermore, translational efforts to identify resistance mechanisms to TTZ are mandatory to guide future personalized strategies in this subset of HER2+ aGEC.