Neoadjuvant chemoradiotherapy plus PD-1 inhibitor (tislelizumab) for high risk and MRF+ low locally advanced rectal cancer.

e15644 Background: PD-1 inhibitors combined with chemoradiotherapy have shown preliminary efficacy in the neoadjuvant treatment of MSS rectal cancer, including improved pathologic complete response (pCR) and major pathological response (MPR) rate. Sufficient tumor regression may provide more opportunities for R0 resection and watch and wait (W&W) for patients who are initially diagnosed with high risk and MRF positive low locally advanced rectal cancer. Therefore, we designed this study to provide sufficient evidence for the efficacy and safety of neoadjuvant therapy for PD-1 in the above patients. Methods: Patients with at least one of the following factors: T3-4, N positive, EMVI positive, MRF positive, lateral lymph node metastasis or low rectal cancer with a risk of sphincter preservation are included. Patients receive neoadjuvant chemoradiotherapy (50Gy/25f with concurrent oral capecitabine) and PD-1 inhibitor tislelizumab followed by 2 cycles of consolidation therapy with CapeOX in combination with tislelizumab. The primary endpoint was pCR rate, and the secondary endpoint were MPR rate, complete response (CR) rate and adverse event. Results: From Jun/2023 to Jun/2024, a total of 29 patients were recruited with a median age of 64 (range 33-78). The median distance of the lower edge of the tumor from the anal verge was 4.1 (1.5-9) cm with 72.4%(21) tumors located within 6 cm of the anal verge. 41% were EMVI positive and 72% were MRF positive. All patients have completed preoperative 4 cycles treatment as planed. The overall CR rate was 41.83%. 23 underwent surgery, the pCR rate was 34.78%, R0 resection rate was 91.3%. 6 patients opted for W&W due to cCR. There were 15 patients with MRF positive and tumors located within 6 cm of the anal verge who were initially considered difficult for resection. All patients received surgery and pCR rate was 46.67%. The average reduction in the maximum diameter of the tumor is 2.4 cm, with the proportion of T1-2 increasing from 0 to 60%. The R0 resection rate reaches 100%, and the rate of sphincter-preserving surgery is 89%. The incidence of TRAEs was 75.86% (22/29) with Leukopenia being the most common (20/22), No grades 3–5 TRAEs were observed. Conclusions: For patients with hish-risk and MRF+ low locally advanced rectal cancer, the addition of PD1 inhibitors to neoadjuvant long-course chemoradiation increases pCR rate, meanwhile raises no significant safety concerns.