Increased assessment of HER2 in metastatic gastroesophageal cancer patients: a nationwide population-based cohort study

Abstract

Background Addition of trastuzumab to first-line palliative chemotherapy in gastroesophageal cancer patients with HER2 overexpression has shown to improve survival. Real-world data on HER2 assessment and administration of trastuzumab are lacking. The aim of this study was to assess HER2 testing, trastuzumab administration, and overall survival (OS) in a nationwide cohort of metastatic gastroesophageal cancer patients. Methods Data of patients with synchronous metastatic gastroesophageal adenocarcinoma diagnosed in 2010-2016 that received palliative systemic treatment (n = 2846) were collected from the Netherlands Cancer Registry and Dutch Pathology Registry. The ToGA trial criteria were used to determine HER2 overexpression. Proportions of HER2 tested patients were analyzed between hospital volume categories using Chi-square tests, and over time using trend analysis. OS was tested using the Kaplan Meier method with log rank test. Results HER2 assessment increased annually, from 18% in 2010 to 88% in 2016 (P < 0.01). Median OS increased from 6.9 (2010-2013) to 7.9 months (2014-2016; P < 0.05). Between the hospitals, the proportion of tested patients varied between 29-100%, and was higher in high-volume hospitals (P < 0.01). Overall, 77% of the HER2 positive patients received trastuzumab. Median OS was higher in patients with positive (8.8 months) and negative (7.4 months) HER2 status, compared to non-tested patients (5.6 months; P < 0.05). Conclusion Increased determination of HER2 and administration of trastuzumab have changed daily practice management of metastatic gastroesophageal cancer patients receiving palliative systemic therapy, and possibly contributed to their improved survival. Further increase in awareness of HER2 testing and trastuzumab administration may improve quality of care and patient outcomes.

Hospital volume and beyond first-line palliative systemic treatment in metastatic oesophagogastric adenocarcinoma: A population-based study

“…In recent years, studies in the curative setting showed that oesophagogastric cancer patients treated in high-volume hospitals have a higher chance of receiving treatment, and better outcomes [14,15,21e25]. Our study adds to the increasing body of evidence that this finding also applies in the metastatic setting [13,18]. Clearly, the simple fact that a patient received treatment could explain the improved survival in high-volume centers, as beyond first-line treatment has been shown to improve survival compared to best supportive care [9,10].…”

“…The rise of beyond first-line treatment use could also be a result of a better performance status in patients after first-line treatment as a result of increased efficacy, e.g. due to the rise in the administration of trastuzumab-containing regimens and decrease in monotherapy use [18], or less toxicity in first line, e.g. due to the increase in doublet and decrease in triplet chemotherapy administration [6].…”

“…Patient, tumour and treatment characteristics were extracted from medical records by specially trained registrars. Human epidermal growth factor receptor 2 (HER2) data were retrieved from PALGA [18]. Data on vital status were obtained by annual linkage to the Dutch Personal Records Database and updated until February 1, 2020.…”

Use of Palliative Chemotherapy and ICU Admissions in Gastric and Esophageal Cancer Patients in the Last Phase of Life: A Nationwide Observational Study

“…Second, to explore whether hospital experience with chemotherapy prescription per se is associated with the outcome indicators, we used a broader treatment experience measure not limited to deceased or palliative patients. For this broader experience measure, the volume of all gastroesophageal cancer patients that received systemic treatment in a curative setting or palliative systemic therapy was calculated, as described earlier [ 16 ]. With the aim to reflect current practice, the volume of recent years (2017 and 2018) was used.…”

<p>USP8 Inhibitor Suppresses HER-2 Positive Gastric Cancer Cell Proliferation and Metastasis via the PI3K/AKT Signaling Pathway</p>

“…17 It is widely known to all that HER-2 is the most close member related to GC progression. 25 HER-2 is a protooncogene encodes cell-membrane associated proteins erb-b2 receptor tyrosine kinase 2 (ErbB2), which is expressed ubiquitously in all cells and the mutation of this gene is responsible for continuous downstream signaling activation, uncontrolled gene amplification and protein expression in tumor cell, inhibition of programmed cell death, formation of tumor angiogenesis, acceleration of tumor invasion force, weakening the immune system, etc. 26,27 In this context, as a drug target for GC, the relationship between USP8 and HER-2 is worth exploring.…”