Dados do Trabalho

Título

HER2 POSITIVE VERSUS HER2-LOW IN METASTATIC GASTRIC CANCER PATIENTS: A PAIRED ANALYSIS FOR PROGNOSTIC BIOMARKER EVALUATION.

Introdução

Gastric/gastroesophageal junction cancer (G-GEJC) is the sixth cause of cancer-related death worldwide. For metastatic G-GEJC (mG-GEJC), the predictive value of HER2 positive (HER2+) and HER2-low (HER2l) is well defined. However, the prognostic role of HER2+ is controversial and data on HERl are scarce.

Objetivo

To compare overall survival (OS) between HER2+ and HER2l patients (pts) with mG-GEJC; to compare first-line (1L) progression-free survival (PFS) between the groups and to analyze prognostic factors.

Método

This retrospective unicentric study recruited pts with mG-GEJC HER2+. A control group of HER2l pts was paired in 1:1 ratio by the nearest neighbor propensity score matching method, using the following pairing categories: gastric vs. GEJC; intestinal vs. diffuse subtype; visceral vs. non-visceral metastasis (mets). Primary tumor/mets samples were tested for HER2 by immunohistochemistry (IHC) with Ventana anti-HER2/neu kit, using the ASCO/CAP criteria for gastric cancer. In situ hybridization (ISH) was done when 2+IHC was detected. HER2+ was defined by 3+IHC or 2+ amplified by ISH and HER2l by IHC 1+ or 2+ non-amplified. Kaplan-Meier curves and Log-Rank test were used for survival analysis. Cox regression was used for uni and multivariate analyses.

Resultado

Between June 2008 and July 2020, 96 pts were recruited (48 in each group). The median follow-up was 36 months (m) and median age at diagnosis was 60 years. Characteristics were well-balanced between HER2+/HER2l groups: the majority were men, caucasian, de novo metastatic, with intestinal-type gastric cancer. 77.1% had visceral mets and 1L anti-HER2 therapy was offered to 66.7% of HER2+ pts. The mean number of 1L cycles was superior for HER2+ (12 vs 7; p=0.01) and median PFS was 7m vs. 5m (HR 0.49; 95%CI 0.31-0.79; p=0.002). There was a trend for superior OS in HER2+ group (14m vs. 10m; HR 0.64; 95%CI 0.39-1.05; p=0.07) and a statistically significant improved OS for 3+IHC versus 1+/2+ (15m vs. 10m; HR 0.57; 95%CI 0.35-0.95; p=0.03). Anti-HER2 therapy numerically increased PFS (8m vs. 5m; p=0.92) and OS (16m vs. 9m; p=0.39) in HER2+ population. Absence of visceral mets and 3+IHC were associated with improved PFS and 3+IHC with improved OS in multivariate analyses.

Conclusão

HER2+ group had a better outcome in 1L PFS, tending to statistically significance in OS when compared to HER2l pts. Some prognostic factors, as 3+IHC and absence of visceral mets were associated with superior results in OS.

Palavras-chave

Metastatic gastric cancer; Low HER2 gastric cancer; Positive HER2 gastric cancer.

Área

Oncologia - Tumores TGI Superior (estômago, esôfago, pâncreas, fígado, vias biliares, duodeno)