47P - Safety and efficacy evaluation of long-course neoadjuvant chemoradiotherapy plus tislelizumab followed by total mesorectal excision for locally advanced rectal cancer: Intermediate results of a multicenter, phase II study

Background

Long course radiotherapy plus neoadjuvant chemotherapy followed by resection (total mesorectal excision, TME) has accepted widespread recognized in the treatment of locally advanced rectal cancer (LARC). Long course (neoadjuvant chemoradiotherapy, NCRT) plus tislelizumab (a PD-1 inhibitor) followed by TME for LARC might bring better downstaging effect and reduce the risk of distant relapse.

Methods

This trial was designed to evaluate the safety and efficacy of LARC patients treated with long course NCRT plus tislelizumab followed by TME. Stage II/III LARC patients with the tumor distal location ≤ 10 cm from anal verge at six centers in China were enrolled. The patients received long course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles capecitabine (1000 mg/m², bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day8), followed by TME 6-8 weeks after the end of radiotherapy. The primary endpoint will be the pathological complete response (pCR) rate.

Results

From 1st June 2021 to 10nd July 2022, 43 patients were enrolled. The median age was 63 (from 32 to 77) years while the median tumor distal location was 5.1 (from 0.1 to 9.9) cm. 30 (29 non-MSI-H/pMMR and 1 MSI-H/dMMR LARC) patients with LARC had undergone TME surgery, with R0 resection rate of 100% and sphincter saving resection rate of 90.0% (27/30). The pCR rate was 43.3 % (13/30) and objective response rate reached 100 % (30/30). Of patients without pCR, 12 (40.0 %) patients reached tumor regression grade 1 according to AJCC standard. 8 (26.7 %) immune-related adverse events including 1 patient with grade 3 diarrhea. Postoperative complications occurred in 3 (10.0 %) of 30 patients, including 1 rectovaginal fistula, 1 anastomotic leakage, and 1 intestinal obstruction, while no treatment-related death occurred.

Conclusions

Tislelizumab added to long course NCRT followed by TME exhibited favorable pCR rate with manageable toxicities and postoperative complication, including non-MSI-H/pMMR LARC. The preliminary results are promising, which provide a potential strategy for neoadjuvant therapy against LARC.

Clinical trial identification

Clinical trial information: NCT04911517.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

China Association of Gerontology and Geriatrics.

Disclosure

All authors have declared no conflicts of interest.