Irae in Phase Iii Study on Neoadjuvant Chemotherapy Versus Perioperative Toripalimab Plus Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma: Hchtog1909

Background In the current era of immunotherapy, there is still no definitive conclusion regarding whether neoadjuvant immunochemotherapy (NAIC) should become the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The HCHTOG1909 study was designed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy followed by MIE. after the complete of recruiment, we tried to fucus on the short term Immune-related adverse events(irAE). Methods This study was a prospective, single-center, open-label, randomized Phase III clinical trial. From May 15, 2020, to April 23, 2024, a total of 401 patients from T1N1–3 M0 to T2–3N0-3M0 (8th UICC-TNM) were enrolled, 196 in toripalimab group and 205 in chemotherapy group. The treatment regimen included paclitaxel (175 mg/m2) and cisplatin (75 mg/m2) plus toripalimab (240 mg) in toripalimab group, or chemotherapy alone group, every 3 weeks for two cycles. After minimally invasive esophagectomy, toripalimab group continued to receive toripalimab (240 mg every 3 weeks for up to 6 months. The primary endpoint was event-free survival (EFS). Results We totally recruied 401 patients (96 women [23.9%]; mean [SD] age, 70.7 [3.5] years; phase III 213 [53.1%] was the morst frequent clinical stages.). Hypothyroidism was the most common irAE. No significant difference was observed in the postoperative complication rate between the two groups (P = 0.453). Additionally, there was no significant difference in the incidence of Grade 3 or 4 treatment-related adverse events, with rates of 13.8% and 10.8% in the respective groups. Conclusion The short term irAE results of HCHTOG1909 showed the addition of perioperative toripalimab to NAC is safe in resectable ESCC.