Abstract
Trastuzumab in combination with a platinum and fluorouracil is the treatment of choice for patients with advanced human epidermal growth factor receptor 2 (HER2) positive gastric cancer and gastroesophageal junction (GEJ) cancer. Pathological assessment of the HER2 status in gastric/GEJ cancer, however, still remains difficult. However, it is a crucial prerequisite for optimal treatment. The GASTRIC-5 registry was designed as an observational, multi-center research initiative comparing local and central HER2 testing. HER2 status was assessed by immunohistochemistry (IHC) and in equivocal cases (IHC score 2+) by additional in-situ hybridization. Between May 2011 and August 2018, tumor samples of 183 patients were tested in local and central pathology laboratories, respectively. Central testing revealed HER2 positivity in 38 samples (21%). Discordant HER2 results were found in 12% (22 out of 183) with locally HER2 positive/centrally HER2 negative results (9%, 17 out of 183), exceeding locally HER2 negative/centrally HER2 positive results (3%, 5 out of 183). Centrally confirmed HER2 positive patients receiving trastuzumab-based palliative first-line therapy showed a longer median overall survival compared to centrally HER2 positive patients not receiving trastuzumab (17.7 months (95% CI: 10,870–24,530) vs. 6.9 months (95% CI: 3.980–9.820), p = 0.016). The findings of the GASTRIC-5 registry corroborate the challenge of HER2 testing in gastric/GEJ cancer and highlight the necessity for central quality control to optimize individual treatment options. Centrally HER2 positive patients not receiving trastuzumab had the worst outcome in a Western real-world gastric/GEJ cancer cohort.
Highlights
Over the last decades, gastric cancer incidence and mortality rates have been continuously declining in Europe [1] and in the United States [2]
In contrast to breast cancer, a benefit for anti-Human epidermal growth factor receptor 2 (HER2) targeting therapy seen with trastuzumab in first-line treatment of HER2 positive gastric/gastroesophageal junction (GEJ) cancer could not be reproduced with other HER2-targeting strategies: no survival benefit was seen with the antibody-drug conjugate trastuzumab emtansine (T-DM1) [14] in second-line, with the tyrosine kinase inhibitor lapatinib in first-line [15] and second-line [16], or with the addition of pertuzumab to trastuzumab and chemotherapy [17] in first-line metastatic HER2 positive gastric/GEJ cancer
This registry was designed by the Austrian Group for Medical Tumor Therapy (AGMT) as an observational, multi-center research initiative in Austria comparing HER2 test results obtained from the local pathology laboratory with a blinded analysis of the HER2 status obtained by a central pathology laboratory
Summary
Gastric cancer incidence and mortality rates have been continuously declining in Europe [1] and in the United States [2]. The phase III “Trastuzumab for Gastric Cancer” ToGA trial demonstrated a statistically significant improvement of median OS from 11.1 to 13.8 months by the addition of the HER2-targeting antibody trastuzumab to a platinum and fluorouracil (5-FU) based doublet chemotherapy in HER2 positive gastric/GEJ cancer [7], and since has become the standard first-line regimen in HER2 positive disease [9,10]. Asian countries face high gastric/GEJ cancer incidence and mortality rates [18,19] and reproducible HER2 results are an absolute necessity in clinical practice. The aim of the GASTRIC-5 registry was to evaluate the rate of HER2 positivity, concordance rate between local and central HER2 results as well as clinical outcome in a real-world Western advanced gastric/GEJ cancer cohort
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