P1.083. Sequential Versus Concurrent Neoadjuvant Immunochemotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: A Randomized, Controlled, Open-Label, Phase II Trial

Abstract

Abstract Topic Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Background Neoadjuvant chemotherapy combined with PD-1 inhibitors has application potential for locally advanced esophageal squamous cell carcinoma (ESCC), but there is no prospective evidence for the optimal timing of the dose (sequential vs. concurrent). Methods This open-label, phase II randomized controlled trial enrolled 70 resectable locally advanced ESCC patients from July 2019 to September 2020 (Phase I) and February 2022 to June 2023 (Phase II), Patients were randomized 1:1 to the sequential group (paclitaxel/cisplatin on day 1, toripalimab on day 3) or the concurrent group (all drugs on day 1). The primary endpoint was the pathological complete remission (pCR), secondary endpoints included major pathologic response (MPR), safety, and 5-year survival (OS/DFS). Results Among 54 surgical patients, Overall pCR was 22.2% (12/54), With no significant difference between the sequential group and the control group (17.8% vs. 26.9%, p = 0.636). Imaging showed an objective response rate (ORR) of 57.1% (40/70), with comparable OS (p = 0.797) and DFS (p = 0.715) between groups. In terms of safety, Grade 3–5 treatment-related adverse events (TRAEs) occurred in 14.2% (10/70), and the incidence of nausea/vomiting and diarrhea was greater in the control group (p < 0.05). There were 6 treatment-related deaths (The control group:5 vs. The sequential group:1). Conclusion There was no significant difference in pCR or survival outcomes between sequential and concurrent immunochemotherapy, but the concurrent strategy led to an increased risk of nausea/vomiting, diarrhea, and fatal immune-related adverse events (irAEs).