A multicenter single-arm trial of sintilimab in combination with chemotherapy for neoadjuvant treatment of resectable esophageal cancer (SIN-ICE study)

Abstract

Background: Preoperative chemotherapy or chemoradiotherapy is the standard treatment for resectable esophageal cancer (EC); however, it is associated with increased postoperative complications and mortality.Recently, Immune Checkpoint inhibitors have been incorporated in the treatment of advanced EC. Its role in the preoperative setting has not been established yet. In this multicenter, single-arm study, we evaluated the efficacy and safety of neoadjuvant therapy with sintilimab in combination with chemotherapy in treating EC.Methods: Patients received neoadjuvant therapy with 3 cycles of sintilimab 200 mg Q3W in combination with platinum-based chemotherapy. Surgery was performed within 4-6 weeks after neoadjuvant therapy. The primary endpoints of the trial were pathological complete response (pCR) and safety.Results: A total of 23 patients (21 men and 2 women) were enrolled. Surgery was completed in 17 participants, with 16 achieving R0 resection and 1 had R1 resection, 5 participants refused surgery. One patient progressed prior to surgery. Twenty one patients (91%) had significant improvement in their dysphagia following treatment as assessed by Stooler's criteria. The majority of patients who underwent resection have a good pathological response and downstaging rate was 76.5% (13/17). A pCR was achieved in 6 cases (6/17, 35.3%) and major pathological response (MPR) in 9 cases (9/17, 52.9%). The main preoperative adverse events (AEs) were vomiting (13/23, 56.5%), leukopenia (12/23, 52.2%), neutropenia (9/23, 39.1%), and malaise (8/23, 34.8%). Immune-related AEs were mild and included hypothyroidism (2/23, 8.7%) and rash (4/23, 17.4%). The incidence of ≥ grade 3 treatment related AEs was 30.4% (7/23). There were no ≥ grade 4 AEs.Conclusions: Sintilimab in combination with chemotherapy in the neoadjuvant treatment of EC is safe and lead to a high pCR. Therefore, further testing is warranted.

Neoadjuvant Pembrolizumab and Chemotherapy in Resectable Esophageal Cancer: An Open-Label, Single-Arm Study (PEN-ICE)

“…Furthermore, in a recent retrospective study that performed two cycles of combination of chemotherapy and immunotherapy in neoadjuvant settings of ESCC, their results revealed a pCR of 22.2% to 35.3%, lower than the pCR in our study. It’s supposed that the cycles of neoadjuvant treatment may affect the efficacy, which deserves further studies to be confirmed ( 15 , 16 ). Moreover, pCR and MPR are verified to confer a survival advantage and to prolong median disease-free survival (DFS) in EC and many other cancers ( 10 ).…”

Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy or chemoradiotherapy in resectable esophageal cancer: A systematic review and meta-analysis

“…The selection process and reasons for study exclusion are shown in Figure 1. Among the 27 studies, 8 trials with 221 patients examined nICRT (14-21), 19 trials with 588 patients examined nICT (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Except one twoarms trial (33), all included studies were single-arm trials.…”

Endoscopic ultrasonography guided cutting scar of esophageal stricture after endoscopic injection sclerotherapy

“…(1) According to the Stooler classification [9,10], the degree of oesophageal stricture was grade II-VI. (2) The diameter of the oesophageal cavity was more than 2.6 mm, so an ultrasonic endoscope could pass.…”

“…The patients were followed up between three to six months: (1) The symptoms would be consultated once a week through the cell phone.We would record the complication (perforation, bleeding, and infection), and degree of the dysphagia of oesophageal stricture [9]. (2) The endoscopy would be performed every three months after treatment.…”

“…According to the Stooler criteria, degree of oesophageal stricture and dysphagia [9,10]: Grade 0: There was no dietary restriction. Grade I: Soft food could be eaten smoothly, and food whose diameter is more than 13 mm could be passed.…”