Huemer Florian, Weiss Lukas, Regitnig Peter, Winder Thomas, Hartmann Bernd, Thaler Josef, Piringer Gudrun, Schmitt Clemens A, Eisterer Wolfgang, Gänzer Hannes, Wüstner Alois, Andel Johannes, Jagdt Björn, Ulmer Hanno, Greil Richard, Wöll Ewald
Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg 5020, Austria.
Salzburg Cancer Research Institute-Center for Clinical Cancer and Immunology Trials (SCRI-CCCIT), Salzburg 5020, Austria.
J Clin Med. 2020 Mar 29;9(4):935. doi: 10.3390/jcm9040935.
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), = 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.
曲妥珠单抗联合铂类和氟尿嘧啶是晚期人表皮生长因子受体2（HER2）阳性胃癌和胃食管交界（GEJ）癌患者的首选治疗方案。然而，对胃/GEJ癌中HER2状态进行病理评估仍然困难。不过，这是优化治疗的关键前提条件。GASTRIC - 5注册研究旨在作为一项观察性、多中心研究项目，比较局部和中心HER2检测。通过免疫组织化学（IHC）评估HER2状态，对于不确定病例（IHC评分为2+），通过额外的原位杂交进行评估。在2011年5月至2018年8月期间，分别在局部和中心病理实验室对183例患者的肿瘤样本进行了检测。中心检测显示38个样本（21%）HER2呈阳性。在12%（183例中的22例）的病例中发现HER2结果不一致，其中局部HER2阳性/中心HER2阴性结果（9%，183例中的17例）超过局部HER2阴性/中心HER阳性结果（3%，183例中的5例）。与未接受曲妥珠单抗治疗的中心HER2阳性患者相比，接受基于曲妥珠单抗的姑息一线治疗的中心确认HER2阳性患者的中位总生存期更长（17.7个月（95%CI：10,870 - 24,530）对6.9个月（95%CI：3.980 - 9.820），P = 0.016）。GASTRIC - 5注册研究的结果证实了胃/GEJ癌中HER2检测的挑战，并强调了进行中心质量控制以优化个体治疗方案的必要性。在西方真实世界的胃/GEJ癌队列中，未接受曲妥珠单抗治疗的中心HER2阳性患者预后最差。
