Local and Central Evaluation of HER2 Positivity and Clinical Outcome in Advanced Gastric and Gastroesophageal Cancer-Results from the AGMT GASTRIC-5 Registry.

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.
Competing Interests: Florian Huemer has received travel grants from Roche. Lukas Weiss received research support from Roche. Peter Regitnig received travel grants from Roche and Novartis Pharma and advisory board honoraria from Roche, Novartis Pharma and Diaceutics. Thomas Winder declares no conflicts of interest, Bernd Hartmann declares no conflicts of interest. Josef Thaler declares no conflicts of interest. Gudrun Piringer received travel grants from Roche. Clemens A. Schmitt declares advisory fees from Roche. Wolfgang Eisterer declares no conflicts of interest. Hannes Gänzer declares no conflicts of interest. Alois Wüstner received travel support from Roche. Johannes Andel received travel grants from Roche. Björn Jagdt declares no conflicts of interest. Hanno Ulmer declares no conflicts of interest. Richard Greil received honoraria, research funding and travel support from Roche and acted as a consultant for Roche. Ewald Wöll declares speaker and advisory fees from Roche.