168 - Immunotherapy Based Total Neoadjuvant Therapy with or without Short-Course Radiotherapy for Locally Advanced Rectal Cancer: Initial Results of TORCH-iTNT

11:15am - 11:25am ET

Room 162

Presenter(s)

Fan Xia, MD, PhD - Fudan University Shanghai Cancer Center, Shanghai, Shanghai

Y. Wang¹, L. Shen¹, J. Wan¹, H. Zhang¹, Y. Wang¹, R. Wu¹, M. L. Zhou¹, W. Yang¹, Y. Chen¹, S. Zhou¹, Z. Zhang¹, J. Wang¹, S. Cai², X. Li², F. Xia¹, and Z. Zhang¹; ¹Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, ²Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

Purpose/Objective(s):

For patients with proficient mismatch repair (pMMR) locally advanced rectal cancer (LARC), combining PD-1 inhibitors with total neoadjuvant chemoradiotherapy (iTNT) has shown significant potential to improve complete response (CR) rates and facilitate organ preservation. However, the combination of radiotherapy and surgery often results in greater functional impairment compared to using either treatment alone. Meanwhile, the synergy between chemotherapy and PD-1 inhibitors has been observed to enhance tumor downstaging, facilitating sphincter-preserving surgery and reducing radiation-related damage. This trial aims to assess the efficacy and functional outcomes of two iTNT regimens: CAPOX combined with PD-1 inhibitor, either with or without short-course radiotherapy (SCRT), in the neoadjuvant treatment of pMMR LARC patients.

Materials/Methods:

The TORCH-iTNT trial is a multicenter phase II randomized trial which enrolled 192 pMMR LARC (T3-4/N+M0) patients. Patients were assigned to either Group A, receiving 6 cycles of CAPOX plus Toripalimab, or Group B, undergoing SCRT (25Gy/5Fx) followed by 6 cycles of CAPOX plus Toripalimab. Patients with clinical complete response (cCR) were offered an option of watch-and-wait (W&W) approach, while non-cCR patients were recommended for surgery. In Group A, adjuvant chemoradiotherapy was administered to patients with positive circumferential margins. The primary endpoint was the complete response (CR) rate, defined as the combination of pathological complete response (pCR) and cCR. Secondary endpoints encompassed organ preservation rate, anorectal function, adverse events, and survival outcomes.

Results:

By January 31, 2026, a total of 192 patients were enrolled, with 148 completing the treatment (70 in Group A and 78 in Group B). Baseline characteristics were well-balanced, and 96.6% (143/148) of patients presented with at least one high-risk feature, including low tumor location (=5 cm), cT4, cN2, MRF+, or EMVI+. Seven patients in Group A and 25 patients in Group B achieved cCR and adopted W&W strategy. Among the 58 and 52 patients in Group A and Group B who received surgery, pCR rates were 32.8% (19/58) and 44.2% (23/52), respectively. Four non-cCR patients in Group A either declined surgery or were still undergoing further treatment. Disease progression was recorded in one patient from each group. The overall CR rates were 37.1% (26/70) in Group A and 61.5% (48/78) in Group B. Thrombocytopenia was the most common grade 3-4 adverse event, occurring in 12.9% of Group A and 14.1% of Group B patients.

Conclusion:

This study is the first comparative analysis of two iTNT regimens in LARC. Unprecedentedly, the neoadjuvant combination of CAPOX and PD-1 inhibitor showed an encouraging CR rate in pMMR LARC patients, and this CR rate can be further enhanced with the addition of SCRT prior to immunochemotherapy. Extended follow-up is essential to evaluate long-term therapeutic efficacy and functional outcomes. (NCT06281405)