PQA 07 - PQA 07 Gastrointestinal Cancer and Sarcoma/Cutaneous Tumors Poster Q&A
3097 - Preoperative Short-Course Radiotherapy Combined with Chemotherapy and Tislelizumab for Locally Advanced Middle-Low Rectal Cancer: A Randomized Phase I/II Clinical Study
W. Li1, H. Yang1, W. Zhou1, B. Feng1, Y. Zhang1, L. N. Zhao2, and L. C. Wei1; 1Department of Radiation Oncology, First Affiliated Hospital of Air Force Medical University, Xian, China, 2Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xian, China
Purpose/Objective(s):This trial was designed to evaluate the safety and efficacy of stage II-III middle-low rectal cancer patients treated with short-course neoadjuvant chemoradiotherapy plus tislelizumab. Materials/
Methods: This is a randomized, open label, phase I/II study. Planed 76 stage II/III mid-to-low locally advanced rectal cancer patients with the tumor distal location =10 cm were randomly assigned (1:1) to tislelizumab group or control group. Eligible patients were aged 18-75 years, histologically or cytologically confirmed rectal adenocarcinoma with microsatellite stable (MSS) or mismatch repair proficient (pMMR). Patients in tislelizumab group received short-course radiotherapy (25 Gy/5 f) and four 21-day cycles capecitabine (1000 mg/m2, bid, po, days 1-14) plus oxaliplatin (130 mg/m2, ivgtt, day1), and tislelizumab (200 mg, ivgtt, day 1). Patients in control group received short-course radiotherapy (25 Gy/5 f) and four 21-day cycles capecitabine (1000 mg/m2, bid, po, days 1-14) plus oxaliplatin (130 mg/m2, ivgtt, day 1). Patients with clinical complete response after neoadjuvant therapy can be managed safely with the watch and wait approach, and others administered surgical resection. The primary endpoint was pathological complete response (pCR) rate. The secondary endpoints include 3-year DFS rate, treatment-related toxicity, and quality of life. Results: Between March 2023 to January 2024, 50 patients were enrolled. 40 patients completed preoperative therapies and 10 were undergoing treatment. The preliminary analysis of 40 eligible patients were randomly assigned to the tislelizumab group (n=21) or the control group (n=19). Main patients characteristics were male of 76.1% (16/21)/52.6% (10/19), tumor distal location =5 cm of 61.9% (13/21)/ 57.9% (11/19), PD-L1 CPS=1 of 57.1% (12/21)/47.4% (9/19) and surgical resection of 47.6% (10/21)/42.1% (8/19) in tislelizumab group/control group. All patients have completed the entire process of short-course radiotherapy. Chemotherapy completion rate was 97.5% and 98.7%, respectively and immunotherapy completion rate was 92.5%. The pCR was 50.0% (5/10) in the tislelizumab group versus 37.5% (3/8) in the control group. Grade 3 treatment-related adverse events (TRAEs) were observed in 3/21 (14.3%) and 4/19 (21.5%) patients in the tislelizumab group and control group, respectively. Only 1 patient suffered from immune-related grade 3 myositis adverse event, which led to treatment interruption. No grade 4-5 TRAEs were observed. Conclusion: For patients with locally advanced rectal cancer, preoperative short-course radiotherapy combined with chemotherapy and PD-1 inhibitor has achieved a high pCR rate, high treatment compliance and low incidence of severe toxic reactions, which worth to be further clinical observed.
