Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: the initial results of a randomized controlled clinical trial (STELLAR II)
10.3760/cma.j.cn112152-20241226-00594
- VernacularTitle:短程放疗序贯化疗和PD-1抑制剂治疗局部晚期直肠癌的随机对照临床研究（STELLAR Ⅱ）初步结果
- Author:
Haoyue LI
1
;
Haitao ZHOU
;
Lichun WEI
;
Yinggang CHEN
;
Wenjue ZHANG
;
Feiyan DENG
;
Ning LI
;
Zheng JIANG
;
Zheng LIU
;
Jianwei LIANG
;
Zhaoxu ZHENG
;
Xianyu MENG
;
Yufei LU
;
Zifa LEI
;
Xiaoge SUN
;
Gong LI
;
Yingjie WANG
;
Yongwen SONG
;
Shunan QI
;
Hao JING
;
Yirui ZHAI
;
Shulian WANG
;
Yexiong LI
;
Yuan TANG
;
Jing JIN
Author Information
1. 国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院放疗科，北京 100021
- Publication Type:Journal Article
- Keywords:
Intestinal neoplasms;
Locally advanced rectal cancer;
Short-course radiotherapy;
Total neoadjuvant therapy;
Immunotherapy;
Complete response;
Toxicity
- From:
Chinese Journal of Oncology
2025;47(9):913-921
- CountryChina
- Language:Chinese
-
Abstract:
Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.
