601P - Short-course radiotherapy based total neoadjuvant therapy combined with PD-1 inhibitor for locally advanced rectal cancer: Preliminary findings of TORCH

Background

For locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) increases the rates of complete response and organ preservation. Hypofractionated radiotherapy shows better synergistic effects in combination with PD-1 inhibitor. The combination of short-course radiotherapy (SCRT) based TNT and PD-1 inhibitor is likely to improve tumor response and prognosis.

Methods

TORCH is a prospective, multicentre, randomized phase II trial. 130 LARC (T3-4/N+M0, distance from anal verge ≤10cm) patients will be treated with TNT and assigned to consolidation arm (A) and induction arm (B). Arm A receives SCRT (25Gy/5Fx) followed by 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Arm B receives 2 cycles of ToriCAPOX followed by SCRT and 4 cycles of ToriCAPOX. TME surgery is scheduled 2 weeks after TNT while a watch and wait (W&W) option can be applied to patients achieving clinical complete response (cCR). The primary endpoint is complete response (CR, pathological complete response [pCR] plus cCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, 3-year DFS rate, etc.

Results

Up to 2023/4/1, 130 patients were recruited and 104 patients have completed the treatment (Arm A 54, Arm B 50). The median age was 55 and 91 patients were stage III. 82.7% (86/104) of them showed one of the following features: lower location (≤5cm), cT4, cN2, MRF+ and EMVI+. 59 patients underwent TME, of which 29 cases achieved pCR (49.2%, 29/59), and the major pathologic response rate (TRG0-1) was 62.7% (37/59). 29 patients achieved cCR and adopted W&W. The total CR rate was 55.8% (58/104), with 57.4% (31/54) in Arm A and 54.0% (27/50) in Arm B. The remaining 16 non-cCR patients refused surgery and went on with close follow-up. Among 53 patients who were assessed N+ on baseline MR and underwent surgery, 48 were pathologically confirmed N0 (90.6%, 48/53). The main grade 3-4 AE was thrombocytopenia (42.3%, 44/104), with 4 cases of grade 4 thrombocytopenia.

Conclusions

For LARC, SCRT based TNT combined with PD-1 inhibitor has achieved a high CR rate, which could provide new choice to achieve organ preservation for MSS and low rectal cancer patients and worth to be further validated in phase III trial.

Clinical trial identification

NCT04518280.

Editorial acknowledgement

None.

Legal entity responsible for the study

Fudan University Shanghai Cancer Center.

Funding

Wu Jie Ping Medical Foundation (grant number HYHX2021010).

Disclosure

All authors have declared no conflicts of interest.