Induction Immunochemotherapy Followed by Concurrent Chemoradiotherapy for Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma (Rice): Preliminary Results

Abstract Background Concurrent chemoradiotherapy (CCRT) is the standard treatment for unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC), but its 5-year OS rate is less than 30%. Neoadjuvant immunochemotherapy (ICT) has shown promising results in resectable LA-ESCC, prompting us to explore its application in unresectable cases by incorporating induction ICT prior to definitive CCRT. We hypothesize that induction ICT can reduce tumor burden and target volume for CCRT, and that early ICT intervention may eliminate micrometastases, thereby improving overall treatment efficacy. This study aims to evaluate the safety and effectiveness of induction ICT followed by CCRT in patients with unresectable LA-ESCC. Methods This phase 2, prospective, single-arm clinical study enrolled patients aged over 18 with untreated, inoperable LA-ESCC. Two cycles of chemotherapy (nab-paclitaxel 200 mg/m2 d1 q3w + carboplatin AUC = 5 d1 q3w) and immunotherapy (PD-1 inhibitor, 200 mg q3w) were administered before CCRT (50.4Gy/28Fx; paclitaxel liposome 50 mg/m2 d1 qw + carboplatin AUC = 2 d1 qw for 5–6 cycles). Consolidation immunotherapy was administered at the discretion of the patient and investigator, for up to one year. The primary endpoint was 2-year OS, with secondary endpoints including safety, PFS, and objective response rate. Safety was evaluated by grade 3 or higher AEs according to CTCAE 5.0. Results Between May 2021 and November 2023, 52 patients were enrolled. Of these, 51 completed 2 cycles of ICT; 45 completed radiotherapy, and 31 completed 5 or more cycles of concurrent chemotherapy. After a median follow-up of 20.5 months, 20 patients had disease progression. The 1- and 2-year PFS rates were 70.3% and 55.8%, and the 1- and 2-year OS rates were 90.1% and 83.4%, respectively. Local recurrence was the most common failure pattern. 13 patients had grade 3 or above AEs during ICT, and 43 during CCRT. Common AEs included lymphopenia, leukopenia, neutropenia, and esophagitis. Conclusion Preliminary findings from the trial suggest that integrating induction ICT prior to CCRT as first-line treatment for unresectable LA-ESCC offers both favorable safety and promising efficacy. Long-term survival benefits will require further follow-up.