Short-course radiotherapy-based total neoadjuvant therapy combined with tislelizumab in the treatment of locally advanced rectal cancer (Neo-STAR): Early outcomes of a prospective, randomized phase II trial.

150 Background: It has been found that radiotherapy possess synergistic anticancer effect with immune checkpoint inhibitors (ICIs). Therefore, this phase II randomized clinical trial (RCT) (ClinicalTrials.gov identifier: NCT05086627) aimed to evaluate the efficacy and safety of SCRT followed by CAPOX and tislelizumab in patients with LARC. Methods: Patients initially diagnosed rectal adenocarcinoma with cT1-2N+M0 or cT3-4NanyM0 were recruited, randomly assigned to receive SCRT (25Gy/5f), followed by four cycles of CAPOX combined with tislelizumab or CAPOX alone, respectively. After total mesorectal excision (TME), two cycles of postoperative adjuvant chemotherapy were given according to the patient's preferences. The pCR rate was set as the primary endpoint, and the major pathological response (MPR) (tumor regression grade (TRG) 0+1), 3-year progression free survival (PFS), 3-year overall survival (OS) and treatment safety were set as the secondary endpoints. R esults: Between September 2021 and March 2024, 118 patients were randomly assigned and 111 patients started allocated treatment, with 53 in the trial group and 58 in the control group. Ninety-six patients (86.5%) completed SCRT and 4 cycles of CAPOX chemotherapy with/without tislelizumab, including 49 patients (92.5%, 49/53) in the trial group and 47 patients (81.0%, 47/58) in the control group. Eighty-two patients (85.4%) had surgical resection, including 42 patients (85.7%, 42/49) in the trial group and 40 patients (85.1%, 40/47) in the control group. Among 82 patients who underwent surgery, 54.8% (23/42) patients in the trial group achieved pCR compared with 37.5% (15/40) in the control group. During the neoadjuvant treatment period, the incidence of grade 3-4 AEs were 9.4% in the trial group and 10.3% in the control group. Conclusions: SCRT-based TNT combined with tislelizumab followed by TME exhibited a favorable pCR rate in LARC. Clinical trial information: NCT05086627 . Surgical and postoperative pathological outcomes. Characteristic Experimental group (n= 42 ) Control group (n=4 0 ) R0 resection Yes 42 (100%) 40 (100%) No 0 (0%) 0 (0%) pCR Yes 23 (54.8%) 15 (37.5%) No 19 (45.2%) 25 (62.5%) TRG score 0 23 (54.8%) 15 (37.5%) 1 3 (7.1%) 2 (5%) 2 14 (33.3%) 15 (37.5%) 3 2 (4.8%) 8 (20%) Pathological T stage T0 24 (57.1%) 15 (37.5%) Tis 1 (2.4%) 0 (0%) T1 0 (0%) 1 (2.5%) T2 9 (21.4%) 6 (15%) T3 6 (14.3%) 10 (25%) T4 2 (4.8%) 8 (20%) Pathological N stage N0 39 (92.9%) 36 (90%) N1 3 (7.5%) 3 (7.5%) N2 0 (0%) 1 (2.5%)