Sintilimab plus cisplatin and nab-paclitaxel induction treatment for locally advanced borderline resectable esophageal squamous cell carcinoma: A single-arm, prospective, phase 2 study (NEOCRTEC2001)

Background: The standard treatment for locally advanced borderline-resectable esophageal squamous cell carcinoma (BR-ESCC) is still debated owing to insufficient evidence from clinical trials. An increasing number of clinical studies focus on investigating the use of immunotherapy in the treatment of esophageal cancer. This phase II trial (NEOCRTEC-2001) aimed to assess the safety and efficacy of sintilimab in combination with cisplatin and paclitaxel induction immunochemotherapy followed by surgery for BR-ESCC. Patients and methods: The NEOCRTEC2001 trial was a single-center, open-label, nonrandomized, phase II study. Patients diagnosed with BR-ESCC were enrolled in the study and initially received 2-4 courses of induction immunochemotherapy at first. The subsequent treatment, surgery or definitive chemoradiotherapy, was determined based on reassessment by MDT. The primary endpoint of the study was the R0 resection rate. Results: From September 2020 to June 2024, a total of 50 eligible patients diagnosed with BR-ESCC were enrolled in the study. All eligible patients underwent induction immunochemotherapy as the initial treatment. After induction immunochemotherapy, 35 of 50 patients (70.0%) were considered resectable, and 29 patients (58.0%) underwent surgery. R0 resection was achieved in 28 patients (56.0%, 95% CI, 41.4 - 69.1%), and 9 patients (18.0%) achieved pathological complete response. AEs of Grade 3 or higher were observed in 8 patients (8/50, 16.0%). Postoperative complications of Grade 3 or higher were observed in 6 patients (6/29, 20.69%). Patients in the R0 resection group demonstrated significantly superior overall survival (OS) and progression-free survival (PFS) than those in the non-R0 group (OS: not reached vs. 19.84 months; HR 0.26; 95%CI 0.07-0.95, p=0.005; PFS: not reached vs. 19.82 months; HR 0.33; 95%CI 0.10-1.11 , p=0.02). Conclusion: In conclusion, the primary endpoint of this trial has not been achieved. Nevertheless, the treatment strategy of induction immunochemotherapy followed by surgery resulted in significant tumor downstaging and a significant pathological complete response rate. Patients who achieved R0 resection exhibited improved survival outcomes. Subsequent studies should focus on optimizing the management of toxicity associated with induction therapy regimens.