Yang Weina, Qian Chengyuan, Luo Jiamin, Chen Chuan, Feng Yan, Dai Nan, Li Xuemei, Xiao He, Yang Yuxin, Li Mengxia, Li Chunxue, Wang Dong
Cancer Center, Daping Hospital, Army Medical University, No.10 Changjiang Zhi Road, Daping Yuzhong District, Chongqing 400042, China.
Department of Oncology, Chongqing University Jiangjin Hospital, Chongqing University, Chongqing 402260, China.
Transl Oncol. 2024 Dec;50:102154. doi: 10.1016/j.tranon.2024.102154. Epub 2024 Oct 13.
Intravenous immune checkpoint inhibitors (ICIs) have shown efficacy in treating locally advanced rectal cancer (LARC), but concerns about systemic toxicity persist. This study developed a unique approach termed chemo-immuno-embolization with transcatheter rectal arterial intervention (CIETAI), aiming to enhance the anti-tumor response while minimizing systemic toxicity.
This is a prospective, single-arm, phase II clinical trial conducted in Daping hospital. Patients with previously untreated stage II/III LARC underwent preoperative CIETAI combined with PD-1 inhibitor tislelizumab plus oxaliplatin, followed by standard concomitant chemoradiotherapy (capecitabine and 50.4 Gy radiation). Intravenous tislelizumab was administered for an additional two cycles.
Between January 2023 and December 2023, a total of 38 patients were enrolled. As the primary endpoint, 17 (44.74 %) patients achieved pathological complete response (TRG0), with a major pathologic response (MPR) rate of 65.79 %. The anal preservation rate was 84.21 % (32/38), and importantly, 15 of 21 patients with low rectal cancer achieved organ preservation with functional maintenance. Eight patients experienced grade 3-4 adverse events (AEs). All immune-related AEs were grade 1-2, with the most common being endocrine toxicity (5/6, 83.33 %). No grade 5 AEs occurred.
This study provides preliminary evidence supporting the safety and efficacy of intraarterial tislelizumab delivery in the neoadjuvant setting for LARC. These promising results encourage further exploration in larger cohorts to validate the clinical impact of this novel CIETAI strategy.
ClinicalTrials.gov Identifier: NCT05957016.
静脉注射免疫检查点抑制剂（ICIs）已显示出治疗局部晚期直肠癌（LARC）的疗效，但对全身毒性的担忧依然存在。本研究开发了一种独特的方法，称为经导管直肠动脉介入化疗免疫栓塞术（CIETAI），旨在增强抗肿瘤反应，同时将全身毒性降至最低。
这是一项在大坪医院进行的前瞻性、单臂、II期临床试验。先前未经治疗的II/III期LARC患者接受术前CIETAI联合PD-1抑制剂替雷利珠单抗加奥沙利铂治疗，随后进行标准同步放化疗（卡培他滨和50.4 Gy放疗）。静脉注射替雷利珠单抗再进行两个周期。
2023年1月至2023年12月，共纳入38例患者。作为主要终点，17例（44.74%）患者达到病理完全缓解（TRG0），主要病理缓解（MPR）率为65.79%。肛门保留率为84.21%（32/38），重要的是，21例低位直肠癌患者中有15例实现了器官保留并维持功能。8例患者发生3-4级不良事件（AE）。所有免疫相关AE均为1-2级，最常见的是内分泌毒性（5/6，83.33%）。未发生5级AE。
本研究提供了初步证据，支持在LARC新辅助治疗中动脉内注射替雷利珠单抗的安全性和有效性。这些有前景的结果鼓励在更大的队列中进一步探索，以验证这种新型CIETAI策略的临床影响。
ClinicalTrials.gov标识符：NCT05957016。
