Interim results from a prospective phase II study of stratified treatment of localized cervical esophageal squamous cell carcinoma by induction immunochemotherapy (SCENIC trial).

4086 Background: Definitive concurrent chemoradiotherapy (dCRT) is the standard treatment for cervical esophageal squamous cell carcinoma (CESCC). However, when dCRT fails, salvage esophagectomy is technically challenging. Moreover, optimizing patient selection for dCRT remains an unresolved concern. We propose a stratified screening strategy by incorporating induction immunochemotherapy, aiming to identify suitable candidates for organ-sparing dCRT and timely surgical treatment. Methods: This prospective interventional phase II study (SCENIC, ChiCTR2200057732) enrolled patients with clinical stage T 2-4 N any M0 (AJCC TNM 8th) resectable CESCC. Eligible participants received induction therapy (IT) of intravenous PD-1 inhibitor tislelizumab (200mg, day 1) plus nab-paclitaxel (100 mg/m 2 , day 1,8,15) and carboplatin (area under curve of 5 mg/mL/min, day 1), administered over two 3-week cycles. Four weeks after IT, treatment response was evaluated via endoscopy and PET-CT. Patients were then divided into 3 groups: remarkable response (RR); limited partial response (LPR); and poor response (POR). RR patients received dCRT, while LPR and POR patients underwent radical surgery. Tislelizumab was maintained after dCRT in RR patients, and postoperative adjuvant therapy was dependent on the patient’s condition, including chemotherapy, radiotherapy, immunotherapy, or follow-up. The primary endpoint is 2-year event-free survival (EFS). Results: From Jul 2022 to Sep 2024, 42 patients were enrolled, with 40 completing two-cycle IT and response evaluation. Post-IT responses were RR in 62.5% (25/40), LPR in 25.0% (10/40), and POR in 12.5% (5/40). All RR patients received subsequent dCRT. In 11 non-RR patients,7 underwent total phryngo-laryngo-esophagectomy(TPLE), 4 received dCRT. Overall, 40 patients (96.0%) had any-grade treatment-related adverse events with leukocytopenia being most prevalent. 5 patients (12.5%) had adverse events of grade 3 or worse. With a median follow-up of 22.3 months (range, 4.5-40.9 months), 2-years EFS rate and overall survival (OS) rate in ITT population was 60.9% and 76.6%. 2-years EFS rate and OS rate in RR group and non-RR group is 78.8% vs 28.0%(p = 0.0011) and 84.8% vs 70.1%(p = 0.0703), respectively. Conclusions: The 2-year survival of RR patients with dCRT followed by IT appears promising compared to historical data. This stratified strategy of induction immunochemotherapy is effective in identifying candidates suitable for dCRT in patients with resectable CESCC. Clinical trial information: ChiCTR2200057732.