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HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer

Cited 177 time in Web of Science Cited 184 time in Scopus
Authors
Van Cutsem, Eric; Bang, Yung-Jue; Feng-Yi, Feng; Xu, Jian M.; Lee, Keun-Wook; Jiao, Shun-Chang; Chong, Jorge Leon; Lopez-Sanchez, Roberto I.; Price, Timothy; Gladkov, Oleg; Stoss, Oliver; Hill, Julie; Ng, Vivian; Lehle, Michaela; Thomas, Marlene; Kiermaier, Astrid; Rueschoff, Josef
Issue Date
2015-07
Citation
Gastric Cancer, Vol.18 No.3, pp.476-484
Keywords
Gastric cancerHER2 testingImmunohistochemistryIn situ hybridizationTrastuzumab
Abstract
In the Trastuzumab for GAstric cancer (ToGA) study, trastuzumab plus chemotherapy improved median overall survival by 2.7 months in patients with human epidermal growth factor receptor 2 (HER2)-positive [immunohistochemistry (IHC) 3+/fluorescence in situ hybridization-positive] gastric/gastroesophageal junction cancer compared with chemotherapy alone (hazard ratio 0.74). Post hoc exploratory analyses in patients expressing higher HER2 levels (IHC 2+/fluorescence in situ hybridization-positive or IHC 3+) demonstrated a 4.2-month improvement in median overall survival with trastuzumab (hazard ratio 0.65). The ToGA study provides the largest screening dataset available on HER2 overexpression/amplification in this indication. We further analyzed correlation(s) of HER2 overexpression/amplification with clinical and epidemiological factors. HER2-positivity was analyzed by histological subtype, tumor location, geographic region, and specimen type. Exploratory efficacy analyses were performed. The HER2-positivity rate was 22.1 % across analyzed tumor samples. Rates were similar between European and Asian patients (23.6 % vs. 23.9 %), but higher in intestinal- vs. diffuse-type (31.8 % vs. 6.1 %), and gastroesophageal junction cancer versus gastric tumors (32.2 % vs. 21.4 %). Across all IHC scores, variability in HER2 staining (a parts per thousand currency sign30 % stained cells) was observed in almost 50 % of cases, with increasing rates in lower IHC categories, and did not affect treatment outcome. The polysomy rate was 4 %. HER2 expression varies by tumor location and type. All patients with advanced gastric or gastroesophageal junction cancer should be tested for HER2 status, preferably using IHC initially. Due to the unique characteristics of gastric cancer, specific testing/scoring guidelines should be adhered to.
ISSN
1436-3291
URI
https://hdl.handle.net/10371/173075
DOI
https://doi.org/10.1007/s10120-014-0402-y
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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