肝动脉灌注化疗联合卡瑞利珠单抗和阿帕替尼作为不可切除肝细胞癌患者的转化治疗：一项单臂探索性试验

Hepatic artery infusion chemotherapy combined with camrelizumab and apatinib as conversion therapy for patients with unresectable hepatocellular carcinoma: a single-arm exploratory trial.

作者信息

Yalikun Kugeluke, Li Zhongchao, Zhang Jianxin, Chang Zhibin, Li Mingming, Sun Zhicheng, Liu Zhaogang, Yang Yue, Xu Lei, Li Lei, Zhang Chengsheng, Sun Pengfei, Zhong Jingtao, Cui Kai, Shi Xuetao, Zhang Bo, Zhao Lei

机构信息

The Affiliated Cancer Hospital of Xinjiang Medical University, 789 Suzhou East Road, Xinshi District, Urumqi, China.

Department of Hepatobiliary Surgery, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Huaiyin District, Jinan, 250117, China.

出版信息

BMC Cancer. 2025 May 7;25(1):838. doi: 10.1186/s12885-025-14250-5.

DOI:10.1186/s12885-025-14250-5

PMID:40335980

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12056981/

Abstract

BACKGROUND

The development of systemic therapy, including targeted drugs and immune checkpoint inhibitors, has significantly improved the prognosis of patients with advanced unresectable hepatocellular carcinoma (uHCC). Hepatic arterial infusion chemotherapy (HAIC) has been gradually applied to the treatment of advanced uHCC, showing good potential as conversion therapy. We aimed to investigate the efficacy and safety of HAIC combined with camrelizumab and apatinib as conversion therapy for uHCC.

METHODS

This study was a single-arm exploratory trial (NCT05099848) in patients with uHCC. Eligible patients received apatinib 250 mg once daily, camrelizumab 200 mg on day 3, and HAIC with FOLFOX regimen (oxaliplatin 85 mg/m at hours 0-2, leucovorin 400 mg/m at hours 2-3, and fluorouracil 400 mg/m at hour 3, followed by fluorouracil 2400 mg/m for 46 h) on days 4-5 of each 21-day cycle for up to 8 cycles. Primary endpoints were conversion rate and margin-free (R0) resection rate.

RESULTS

Between March 2021 and July 2023, 19 patients were enrolled. Median follow-up was 14.9 months (interquartile range, 10.9-21.1). Disease became resectable in 14 (73.7%) of 19 patients; nine (47.4%) patients received R0 resection, while five (26.3%) refused surgery and opted for observation. Three (33.3%) of nine patients with surgery achieved major pathological response, including two (22.2%) with pathological complete response. Objective response and disease control rates were 47.4% (9/19) and 89.5% (17/19) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 and both 89.5% (17/19) per modified RECIST. Survival data were immature. Fourteen (73.7%) of 19 patients had grade 3 or higher treatment-related adverse events, with the most common being increased alanine aminotransferase or aspartate aminotransferase (seven [36.8%]) and increased lymphocyte count (six [31.6%]). No treatment-related deaths occurred.

CONCLUSIONS

The combination of HAIC, camrelizumab, and apatinib as conversion therapy shows promising clinical benefits and a manageable safety profile in patients with uHCC. Future randomized controlled trials are warranted.

TRIAL REGISTRATION

ClinicalTrials.gov NCT05099848. Registered on October 13, 2021.

摘要

背景

包括靶向药物和免疫检查点抑制剂在内的全身治疗的发展，显著改善了晚期不可切除肝细胞癌（uHCC）患者的预后。肝动脉灌注化疗（HAIC）已逐渐应用于晚期uHCC的治疗，显示出作为转化治疗的良好潜力。我们旨在研究HAIC联合卡瑞利珠单抗和阿帕替尼作为uHCC转化治疗的疗效和安全性。

方法

本研究是一项针对uHCC患者的单臂探索性试验（NCT05099848）。符合条件的患者接受阿帕替尼每日一次250mg、第3天接受卡瑞利珠单抗200mg，并且在每21天周期的第4 - 5天接受HAIC联合FOLFOX方案（奥沙利铂85mg/m²在0 - 2小时、亚叶酸钙400mg/m²在2 - 3小时、氟尿嘧啶400mg/m²在3小时，随后氟尿嘧啶2400mg/m²持续46小时），最多进行8个周期。主要终点是转化率和无瘤（R0）切除率。

结果

2021年3月至2023年7月期间，共纳入19例患者。中位随访时间为14.9个月（四分位间距，10.9 - 21.1）。19例患者中有14例（73.7%）疾病变为可切除；9例（47.4%）患者接受了R0切除，而5例（26.3%）患者拒绝手术并选择观察。9例接受手术的患者中有3例（33.3%）达到主要病理缓解，包括2例（22.2%）达到病理完全缓解。根据实体瘤疗效评价标准（RECIST）1.1版，客观缓解率和疾病控制率分别为47.4%（9/19）和89.5%（17/19），根据改良RECIST标准两者均为89.5%（17/19）。生存数据尚不成熟。19例患者中有14例（73.7%）发生3级或更高等级的治疗相关不良事件，最常见的是丙氨酸氨基转移酶或天冬氨酸氨基转移酶升高（7例[36.8%]）和淋巴细胞计数增加（6例[31.6%]）。未发生治疗相关死亡。