Loss of HER2 positivity after anti-HER2 chemotherapy in HER2-positive gastric cancer patients: results of the GASTric cancer HER2 reassessment study 3 (GASTHER3).

BACKGROUND: Although discordance in HER2 positivity between primary and metastatic lesions is well established, changes in HER2 positivity after anti-HER2 therapy have not been well evaluated in gastric cancer. We aimed to evaluate whether HER2 expression in gastric cancer is affected by trastuzumab therapy. METHODS: We enrolled 48 HER2-positive advanced gastric cancer patients treated with trastuzumab-containing first-line chemotherapy and had paired biopsies at baseline and after progression. RESULTS: At baseline, HER2 was positive, with immunohistochemistry (IHC) 2+ and in situ hybridization (ISH)+ in five patients, and with IHC 3+ in 43 patients. Fourteen patients (29.1%) exhibited loss of HER2 positivity on post-progression biopsy: 10 with IHC 0 or 1+, and four with IHC 2+/ISH-. HER2 remained positive on second biopsy in 34 patients: four with IHC 2+/ISH+, and 30 with IHC 3+. Median H-scores decreased from 225 to 175 (p = 0.047). HER2 genetic heterogeneity was defined in one of 34 ISH-assessable patients (2.9%) at baseline and seven of 32 (21.9%) at second biopsy. Among 13 patients who received second-line trastuzumab emtansine, three showed HER2-negative conversion; they had no objective response and short progression-free survival (1.2, 1.3, and 3.4 months). Patients with stable HER2 status had a 44% response rate and median progression-free survival of 2.7 (0.4-36.8) months. CONCLUSION: A substantial portion of HER2-positive patients showed HER2-negative conversion with increased HER2 genetic heterogeneity after failure of trastuzumab-containing chemotherapy. Loss of HER2 positivity could be predictive of second-line anti-HER2 treatment, suggesting a need to reexamine HER2 status before initiating second-line anti-HER2 therapy.

Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018.

Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the 'gold standard' of management, treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.