TY - JOUR

T1 - Changing HER2-status of the primary gastric tumor after neoadjuvant trastuzumab-based therapy

AU - Orlova, Rashida

AU - Beliak, Natalia P.

AU - Kutukova, Svetlana

AU - Zhukova, Natalia V.

AU - Avramenko, Inna V.

AU - Popova, Natalia V.

AU - Ivanova, Anastasia

AU - Androsova, Alexandra

AU - Zorina, Ekaterina

N1 - DOI: 10.1200/JCO.2020.38.15_suppl.e16529 Journal of Clinical Oncology 38, no. 15_suppl

PY - 2020

Y1 - 2020

N2 - Background: Aproximetly 16 % of patients with metastatic gastric cancer (GC) have HER2+ tumors. With localized stages, the detection rate of HER2+ is known to be lower. Addition of trastuzumab (T) to chemotherapy (CT) improved survival in metastatic, HER2+ GC. Unlike the metastatic disease, Her-2 did not represent an independent prognostic biomarker for early stages during exploratory analysis of MAGIC trial. The aim of the study was to compare human epidermal growth factor receptor 2 (HER2) expression before and after trastuzumab-based chemotherapy in patients with locally advanced HER2-positive gastric cancer, to evaluate the contribution of trastuzumab to the effectiveness of neoadjuvant treatment in this rare patient population. Methods: We assessed HER2 expression using immunohistochemistry in pre-treatment biopsied specimens and post-treatment resected specimens obtained from 10 patients with locally advanced HER2-positive (3+) gastric cancer receiving trastuzumab-based neoadjuvant chemotherapy: 8 men (80%) and 2 women (20%), from 30 to 80 years old, the median age was 63,5 years. Included 7 patients with resectable adenocarcinoma of the stomach and 3 patients with adenocarcinoma of the esophageal-gastric junction. All patients received neoadjuvant therapy with trastuzumab (100%) + chemotherapy: FLOT (2 patients), FOLFOX (7 patients), XELOX (1 patient). All patients underwent R0 gastrectomy. Tumor regression grading (TRG) after treatment were determined according to Mandard system. Results: Two patients showed a complete pathomorphological response of the tumor (20%,TRG1), therefore, the determination of postoperative HER2 status was not possible. Two patients (20%) maintained the HER2-positive status and six patients (60%) had a change in HER2 expression from positive to negative. Three patients had a (y)pT3 and 5 had a (y)pN+ tumor. Basing on histological changes the tumor regression TRG3 ( < 10% residual tumor cells) was observed in 5 patients (50%). TRG 4-5(preponderance of tumor cells/tumors without changes of regression) observed in 3 patients (30%). The follow-up period is too short for disease-free survival or overall survival to be assessed. Conclusions: HER2 expression can change after trastuzumab-based chemotherapy in patients with locally advanced HER2-positive gastric cancer. Continuous monitoring of HER2 expression after neoadjuvant treatments may be utilized to determine whether the continued use of trastuzumab is advisable.

AB - Background: Aproximetly 16 % of patients with metastatic gastric cancer (GC) have HER2+ tumors. With localized stages, the detection rate of HER2+ is known to be lower. Addition of trastuzumab (T) to chemotherapy (CT) improved survival in metastatic, HER2+ GC. Unlike the metastatic disease, Her-2 did not represent an independent prognostic biomarker for early stages during exploratory analysis of MAGIC trial. The aim of the study was to compare human epidermal growth factor receptor 2 (HER2) expression before and after trastuzumab-based chemotherapy in patients with locally advanced HER2-positive gastric cancer, to evaluate the contribution of trastuzumab to the effectiveness of neoadjuvant treatment in this rare patient population. Methods: We assessed HER2 expression using immunohistochemistry in pre-treatment biopsied specimens and post-treatment resected specimens obtained from 10 patients with locally advanced HER2-positive (3+) gastric cancer receiving trastuzumab-based neoadjuvant chemotherapy: 8 men (80%) and 2 women (20%), from 30 to 80 years old, the median age was 63,5 years. Included 7 patients with resectable adenocarcinoma of the stomach and 3 patients with adenocarcinoma of the esophageal-gastric junction. All patients received neoadjuvant therapy with trastuzumab (100%) + chemotherapy: FLOT (2 patients), FOLFOX (7 patients), XELOX (1 patient). All patients underwent R0 gastrectomy. Tumor regression grading (TRG) after treatment were determined according to Mandard system. Results: Two patients showed a complete pathomorphological response of the tumor (20%,TRG1), therefore, the determination of postoperative HER2 status was not possible. Two patients (20%) maintained the HER2-positive status and six patients (60%) had a change in HER2 expression from positive to negative. Three patients had a (y)pT3 and 5 had a (y)pN+ tumor. Basing on histological changes the tumor regression TRG3 ( < 10% residual tumor cells) was observed in 5 patients (50%). TRG 4-5(preponderance of tumor cells/tumors without changes of regression) observed in 3 patients (30%). The follow-up period is too short for disease-free survival or overall survival to be assessed. Conclusions: HER2 expression can change after trastuzumab-based chemotherapy in patients with locally advanced HER2-positive gastric cancer. Continuous monitoring of HER2 expression after neoadjuvant treatments may be utilized to determine whether the continued use of trastuzumab is advisable.

UR - https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.e16529

M3 - Meeting Abstract

VL - 38

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 15 suppl

M1 - e16529

ER -