A population-based study in resected esophageal or gastroesophageal junction cancer aligned with CheckMate 577

Abstract

Background: 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). Population-based data can provide insights in outcomes from clinical practice. 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. Patients and Methods: Resected patients with stage II/III esophageal or gastroesophageal junction cancer (2015–2016) treated with neoadjuvant chemoradiotherapy were selected from the Netherlands Cancer Registry. Patients with cervical esophageal cancer, irradical resection, or complete pathological response were excluded. Disease-free and overall survival were assessed from 12 weeks after resection using Kaplan-Meier methods. 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. Results: We identified 634 patients. Sixty percent of patients were diagnosed with recurrence or were deceased at the end of follow-up. Median disease-free survival was 19.7 months and median overall survival was 32.2 months. After the matching procedure, the median disease-free survival was 17.2 months and median overall survival was 28.2 months. Conclusions: Disease-free survival in our population-based study was considerably longer than the placebo population of CheckMate-577 (19.7 versus 11.0 months). Possible explanations are differences in characteristics, quality of esophageal cancer care, or differential strategies for evaluation of recurrence. 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. The difference in postoperative imaging could partially explain the longer disease-free survival observed in our study. Quality and optimization of current treatment modalities remain important aspects of esophageal cancer care.

Pivotal role of myeloid‐derived suppressor cells in infection‐related tumor growth

“…21 For example, patients with PIC may more effectively benefit from adjuvant chemotherapy with anti-PD-L1 antibody. 52 This study has some limitations. In the clinical setting, a relatively small number of patients were included in this study, and the study was also retrospective in nature.…”

“…Thus, we believe that targeting PD‐L1 + MDSCs induced by infection may be an effective treatment strategy in patients with PIC 21 . For example, patients with PIC may more effectively benefit from adjuvant chemotherapy with anti‐PD‐L1 antibody 52 …”

Radiotherapy combined with immune checkpoint inhibitors in locally advanced/metastatic esophageal squamous cell carcinoma: clinical trials, efficacy and future directions

“…However, some scholars have questioned the apparently shorter DFS time observed in the placebo group of CheckMate 577. A retrospective study in the Netherlands collected esophageal patients meeting the inclusion criteria of CheckMate 577 but not receiving adjuvant Nivolumab, revealing a median DFS of 19.7 months, which was much longer than that in placebo population of CheckMate 577 ( 58 ). It is also noteworthy that ESCC accounted for only 29% of participants in CheckMate 577, and no DFS benefit was observed in the Asian population or Asia region subgroup ( 42 ).…”

Efficacy and adverse events of immune checkpoint inhibitors in esophageal cancer patients: Challenges and perspectives for immunotherapy

“…62 In the CheckMate-577 study (the world's first phase III study of postoperative adjuvant therapy for ECs), improved disease-free survival was observed. 20,63 In the Attraction-02 and Attraction-03 clinical trials, immunotherapy was further proven to bring significant clinical benefits. In the ATTRACTION-3 trial, nivolumab significantly improved the OS compared with chemotherapy (median OS 10.9 vs. 8.4 months) in the treatment of ESCC.…”

“…The ORR of pembrolizumab in combination with chemotherapy was 45.0% in the KEYNOTE‐590 study 62 . In the CheckMate‐577 study (the world's first phase III study of postoperative adjuvant therapy for ECs), improved disease‐free survival was observed 20,63 . In the Attraction‐02 and Attraction‐03 clinical trials, immunotherapy was further proven to bring significant clinical benefits.…”