

Although the question remains whether additional treatment with chemotherapy should be provided in the adjuvant setting, subgroups such as patients with ERCC1 negativity could potentially benefit from adjuvant SOX based on our exploratory biomarker research. To conclude, six cycles adjuvant S-1 and oxaliplatin were not feasible in pretreated esophageal adenocarcinoma. Moreover, 5-FU pharmacokinetics significantly correlated with treatment-related toxicity. Our protein signature model was predictive of survival. Patients with ERCC1 negative tumor expression had significantly better survival compared to ERCC1 positivity (p = 0.01). Survival was not significantly prolonged compared to a matched cohort (p = 0.09). The median recurrence-free and overall survival were 28.3 months and 40.8 months, respectively (median follow-up 29.1 months). The main reason for early discontinuation was toxicity (67%). Median dose intensity was 98% for S-1 and 62% for oxaliplatin. Forty patients were enrolled and 48% completed all adjuvant cycles. We performed exploratory propensity-score matching to compare survival, ERCC1 and Thymidylate Synthase (TS) immunohistochemistry analyses, proteomics biomarker discovery and 5-FU pharmacokinetic analyses. The primary endpoint was feasibility, defined as ≥50% completing treatment. Patients treated with nCRT (paclitaxel, carboplatin) and esophagectomy received six 21-day cycles with oxaliplatin (130 mg/m2) on day 1 and S-1 (25 mg/m2 twice daily) on days 1–14. We assessed the feasibility of adjuvant S-1 and oxaliplatin following neoadjuvant chemoradiotherapy (nCRT) and esophagectomy.

Quality and optimization of current treatment modalities remain important aspects of esophageal cancer care. The difference in postoperative imaging could partially explain the longer disease-free survival observed in our study. In the Netherlands postoperative imaging is not part of the standard follow-up as opposed to the standard postoperative imaging in the CheckMate 577 trial. Possible explanations are differences in characteristics, quality of esophageal cancer care, or differential strategies for evaluation of recurrence. After the matching procedure, the median disease-free survival was 17.2 months and median overall survival was 28.2 months.ĭisease-free survival in our population-based study was considerably longer than the placebo population of CheckMate-577 (19.7 versus 11.0 months). Median disease-free survival was 19.7 months and median overall survival was 32.2 months. Sixty percent of patients were diagnosed with recurrence or were deceased at the end of follow-up. In addition, to adjust for differences in characteristics between CheckMate 577 and our population-based cohort, a matching-adjusted indirect comparison was performed for pathological lymph node status and pathological tumor status. Disease-free and overall survival were assessed from 12 weeks after resection using Kaplan-Meier methods. Patients with cervical esophageal cancer, irradical resection, or complete pathological response were excluded. Resected patients with stage II/III esophageal or gastroesophageal junction cancer (2015–2016) treated with neoadjuvant chemoradiotherapy were selected from the Netherlands Cancer Registry. The aim of our study was to investigate disease-free and overall survival in a nationwide population aligned with the inclusion criteria of CheckMate 577. Population-based data can provide insights in outcomes from clinical practice.

Results of CheckMate 577 show an improved disease-free survival for patients with resected esophageal or gastroesophageal junction cancer treated with adjuvant nivolumab compared with placebo (22.4 versus 11.0 months).
