Sintilimab after Concurrent Chemoradiotherapy in Locoregional Recurrent ESCC after Definitive Treatment: A Single-Arm, Phase II Study

Abstract

<h3>Purpose/Objective(s)</h3> After definitive treatment of esophageal cancer, patients are at high risk of recurrence with a subsequent 8-10 months survival time. Chemoradiotherapy (CRT) effectively treats locoregional relapse; however, efficient consolidation therapy is lacking. Sintilimab is a highly selective, humanized, monoclonal antibody against PD-1, which showed a prolonged survival benefit and a favorable safety in advanced esophageal squamous cell carcinoma (ESCC) patients. The study evaluated the efficacy of sintilimab as consolidation therapy in patients with locoregional recurrent ESCC after definitive treatment. <h3>Materials/Methods</h3> This is a single-arm, phase II study. Patients with locoregional recurrent ESCC, who completed CRT without progression, were enrolled and received sintilimab (200mg, iv, Q3W) up to 12 months. Sintilimab was administered 17 to 60 days after the patients had received CRT. The primary endpoint was progression free survival (PFS), and the second endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS). <h3>Results</h3> Between November,2019 to September, 2021, total of 27 patients were enrolled: 22 males (81.5%), median age 63 years (range, 36-76), 25 squamous cell carcinomas (92.6%), 20 stage-IV (74.1%), 27 ECOG PS 1(100%), and 15(55.6%) with smoking history. The median follow-up time was 12.7 months. The median PFS and OS were 8.25 months (95% CI, 3.71-NA) and 15.67 months (95% CI, 7.29-NA). The 6-months and 12-months PFS were 61.7% (95% CI,45.6-83.6) and 35% (95% CI,19.3-63.4). The 6-months and 12-month OS were 77.8% (95% CI,63.6-95.2) and 54.4% (95% CI,38.3-77.3). ORR was 33.3% (95% CI,17.2-54.6), including 1 CR, 6 PR. DCR was 95.2% (95% CI,74.1-99.8). 10 cases of grade 3 or 4 adverse events occurred, including lymphopenia, leukopenia, thrombocytopenia, anemia, and myocarditis, mainly caused by chemoradiotherapy. Two cases of immune related adverse events occurred, including pneumonitis and hypothyroidism. <h3>Conclusion</h3> Sintilimab has been shown encouraging clinical benefits and acceptable safety as the consolidation therapy after CRT for locoregional recurrent esophageal cancer. The long-term efficacy is still under follow-up.