Abstract
Trastuzumab, a monoclonal antibody against HER2, has become standard of care for metastatic HER2-overexpressing esophagogastric adenocarcinoma and is currently investigated as (neo)adjuvant treatment option in HER2-positive esophagogastric adenocarcinoma. The HER2 status is commonly determined on archived material of the primary tumor. However, this status may change over the course of treatment or disease progression. The aim of this study was to assess the dynamics of HER2 status in esophageal adenocarcinoma (EAC) in patients with resectable and recurrent disease, and to determine the associations of these changes with clinical outcome. Discordance, defined as any change in HER2 status between matched biopsy and post-neoadjuvant chemoradiation therapy resection specimen (N = 170), or between matched resection specimen and recurrence of patients not eligible for curative treatment (N = 61), was determined using the standardized HER2 status scoring system. Clinically relevant positive discordance was defined as a change to HER2 positive status, as this would imply eligibility for HER2-targeted therapy. A difference in HER2 status between biopsy and resection specimen and resection specimen and metachronous recurrence was observed in 2.1% (n = 3) and 3.3% (n = 2) of the paired cases, respectively. Clinically relevant discordance was detected in 1.4% (n = 2) of the resectable patients and 1.6% (n = 1) of the patients with recurrent disease. Patients with HER2-positive status tumors before start of neoadjuvant treatment showed better overall survival, but not statistically significant. No association between HER2 status discordance and survival was found. Clinically relevant HER2 status discordance was observed and in order to prevent under-treatment of patients, the assessment of HER2 status in the metastatic setting should preferably be performed on the most recently developed lesions if the previous HER2 assessment on archival material of the primary tumor was negative.
Highlights
Over the past years, an increase in the incidence of esophageal adenocarcinoma (EAC) has been observed in Western countries
A total of 23 of the 170 neoadjuvant chemo(radio) therapy (nCRT) treated patients (13.5%) had complete tumor regression after nCRT (Mandard 1) and no HER2 status could be assessed on the resection material (Table 1). 54.1% (n = 92) had a recurrence after a mean follow-up time of 45 months (standard deviation (SD) 34 months)
In our cohort of patients with resectable disease, a discordance in HER2 status between biopsy and resection specimen was observed in 2.1% of patients that received neoadjuvant treatment
Summary
An increase in the incidence of esophageal adenocarcinoma (EAC) has been observed in Western countries. New multimodality treatment strategies have been established, survival remains disappointing. For patients treated with curative intent, treatment consists of neoadjuvant chemo(radio) therapy (nCRT) followed by esophagectomy [2]. In the Netherlands, the CROSS regimen; weekly administration of paclitaxel and carboplatin for five consecutive weeks with the addition of a fractionated radiotherapy, is standard of care for patients with resectable disease. Prognosis has increased by the addition of this neoadjuvant therapy, survival does not exceed 49 months [3]. Whether anti-HER2 targeted treatment strategies are of added value in patients with resectable EAC is currently being investigated in a phase I/II clinical trial (NCT02120911) [6]
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