564P - Short-course radiotherapy combined with chemotherapy and PD-1 inhibitor in proficient mismatch repair or microsatellite stable (pMMR/MSS) low-lying early rectal cancer: Preliminary findings from a prospective, multi-center, phase II trial (TORCH-E)

Background

Radical surgery is the conventional treatment for stage I-II rectal cancer (cT1-3bN0M0). Emerging research suggests that neoadjuvant radiotherapy combined with immunotherapy enhance tumor regression in pMMR/MSS locally advanced rectal cancer and could enable organ preservation via a "Watch and Wait” (WW) strategy in patients who achieve a clinical complete response (cCR). Therefore, this study investigates the efficacy and safety of integrating radiotherapy, chemotherapy, and PD-1 inhibitor in pMMR/MSS, low-lying early, rectal cancer.

Methods

This is a prospective, multi-center, phase II trial. 34 patients with cT1-3bN0M0 rectal cancer proven pMMR/MSS and located ≤5cm from the anal verge will receive short-course radiotherapy (25 Gy/5 Fx) followed by four cycles of CAPOX chemotherapy and PD-1 antibody Toripalimab. A WW option can be applied to patients achieving cCR while surgery was recommended for those who failed to achieve cCR. The primary endpoint is complete response (CR) which includes pathological complete response after surgery and cCR if WW was applicable. The secondary endpoints include adverse effects rate, disease free survival rate, etc.

Results

Up to April 2024, 26 patients have completed neoadjuvant treatment. The median age was 56.5 years, 76.9% (20/26) patients had T3 disease defined by rectal MRI. Among 26 evaluable patients, 13 achieved cCR and adopted WW. Other 13 patients underwent surgery, within which 6 had local excision and showed no residual tumor cells (ypT0), 7 received total mesorectal excision and 4 confirmed no residual tumor cells from the primary tumor and lymph nodes (ypT0N0, TRG0). Thus, the total CR rate was 88.5% (23/26). Grade 3-4 adverse events occurred in 8 patients, including 7 (26.9%) thrombocytopenia and 1(3.8%) leukopenia, and there were no treatment-related deaths.

Conclusions

The innovative therapeutic approach combining PD-1 monotherapy with SCRT and chemotherapy has achieved a remarkable CR rate of 88.5%, which may offer a promising option for pMMR/MSS, low-lying early rectal cancer patients to achieve organ preservation.

Clinical trial identification

NCT05555888, FDRT-2022-227-2945, Initial Release: 09/22/2022.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Beijing Xisike Clinical Oncology Research Foundation.

Disclosure

All authors have declared no conflicts of interest.