An interim analysis of phase III study on neoadjuvant chemotherapy versus perioperative toripalimab plus neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma: Henan Cancer Hospital Thoracic Oncology Group 1909 (HCHTOG1909)

4076 Background: In the era of immunotherapy, whether neoadjuvant immunochemotherapy (NAIC) would be standard treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is without conclusion. The HCHTOG1909 was aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy followed by MIE. This second interim analysis was aim to compare the short term results of two groups. Methods: A prospective, single-center, open-label, randomized phase III clinical trial. Between May 15, 2020 and April 23, 2024, 401 resectable ESCC with clinical stage T1N1-3M0 to T2-3N0-3M0 were enrolled(8th UICC-TNM), 196 in the toripalimab group and 205 in the chemotherapy group. The patients receive either neoadjuvant paclitaxel (175 mg/m2) and cisplatin (75 mg/m2) plus toripalimab (240mg) (toripalimab group) or paclitaxel and cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After MIE, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The event-free survival (EFS) was the primary endpoint. The pathological complete response (pCR) was the key secondary endpoints. Other endpoints included postoperative complications, mortality, adverse events, overall survival and disease free survival. We planned 3 interim analyses. This was a planned second interim analysis. The sample size was calculated based on the primary endpoint EFS. The hazard ratio assumed to be 0.68 between two groups. A type I error allocated (two-sided) 0.05, 90% power and drop-out rate of 10% in 5 years. The χ 2 test and the Fisher exact test was employed for categorical parameters, the t test or analysis of variance was adopted for continuous variables. Results: Among 401 patients ( 305 men [76.1%]; mean [SD] age, 70.7 [3.5] years; most frequent clinical stages III 213 [53.1%] ). The toripalimab group had a higher pCR rate (26.1% vs. 6.2%; P < 0.001). The 90-day perioperative mortality rate was 2.42%(4) for the toripalimab group and 2.5%(4) for the chemotherapy alone group ( P = 0.9790). The most frequent irAE was hypothyroidism. There was no significant difference observed for postoperative complication rate ( P = 0.453). The grade 3 or 4 treatment-related adverse events did not differ between the two groups (13.8% versus 10.8%). Conclusions: The interim results of HCHTOG1909 showed the addition of perioperative toripalimab to NAC is safe in resectable ESCC, and the pCR rate is significantly improved. Clinical trial information: NCT04280822 .