Preliminary results from the multicenter, randomized phase III trial (SCIENCE): Comparing chemotherapy plus sintilimab and chemoradiotherapy plus sintilimab versus chemoradiotherapy for neoadjuvant treatment in resectable locally advanced esophageal squamous cell carcinoma.

Abstract

LBA329 Background: Neoadjuvant chemotherapy (nCT) or chemoradiotherapy (CRT) followed by surgery is the standard treatment for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). Despite significant advancements in therapeutic strategies, the rate of recurrence remains high. Therefore, this multicenter, randomized, Phase III trial (SCIENCE) aims to evaluate and compare the efficacy of nCT and nCRT plus Sintilimab, and nCRT alone in patients with resectable LA-ESCC. Methods: Eligible patients with thoracic ESCC and had not received any prior treatment. Patients were clinically staged as locally advanced (cT1N2-3M0 or cT2-4aN0-3M0). Participants were randomized in a 1:1:1 ratio to one of three neoadjuvant treatment groups: Group A: Sintilimab combined with nCT (nab-paclitaxel plus carboplatin) for two cycles. Group B: Sintilimab combined with concurrent nCRT (nab-paclitaxel plus carboplatin chemotherapy and radiotherapy using IMRT/IGRT totaling 41.4 Gy). Group C: Concurrent nCRT alone. Surgical resection was planned 6-8 weeks after the completion of neoadjuvant therapy. The co-primary endpoints were pathological complete response (pCR) rate, and event-free survival (EFS), evaluated by investigators according to RECIST 1.1 criteria. Results: Between November 2022 and June 2024, 146 patients were enrolled and randomized into three groups: Group A (n = 46), Group B (n = 45), and Group C (n = 55). The majority of patients were male (89.7%; 131/146), with most clinical stage III disease (72.6%; 106/146) and tumors located in the middle thoracic esophagus (51.4%; 75/146). All patients completed the neoadjuvant treatment and underwent surgical resection and achieving a 100% R0 resection rate. The pCR rates differed significantly among the groups, with Group A achieving a pCR rate of 13%, Group B 60%, and Group C 47.3%. Both Group B and C demonstrated significantly higher pCR rates compared to Group A, with Group B versus Group A showing a difference of 47% (95% CI, 27.8–62.2; OR = 10; 95% CI, 3.7–30.8; P < 0.0001) and Group C versus Group A showing a difference of 34.2% (95% CI, 16.4–49.1; OR = 6; 95% CI, 2.3–17.8; P = 0.0005). No perioperative deaths were reported. Treatment-emergent adverse events (TEAEs) of any grade were observed in 50% of patients in Group A, 86.7% in Group B, and 85.5% in Group C. Additionally, the incidence of Grade 3 or higher TEAEs during neoadjuvant treatment was 8.7% in Group A, 31.1% in Group B, and 36.4% in Group C. Conclusion: This Phase III trial demonstrates that nCRT, with or without Sintilimab, significantly enhances pCR rates compared to nCT with Sintilimab in LA-ESCC, without increasing surgical risks. Ongoing monitoring of EFS is necessary to validate these results. Clinical trial information: NCT05244798 .