信迪利单抗联合乐伐替尼用于中/局部晚期肝细胞癌的转化治疗：一项2期研究。
Sintilimab plus Lenvatinib conversion therapy for intermediate/locally advanced hepatocellular carcinoma: A phase 2 study.
作者信息
Wang Lijun, Wang Hongwei, Cui Yong, Liu Ming, Jin Kemin, Xu Da, Wang Kun, Xing Baocai
机构信息
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepatopancreatobiliary Surgery Unit I, Peking University Cancer Hospital & Institute, Beijing, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, Beijing, China.
出版信息
Front Oncol. 2023 Feb 16;13:1115109. doi: 10.3389/fonc.2023.1115109. eCollection 2023.
INTRODUCTION
Patients with intermediate or locally advanced hepatocellular carcinoma (HCC) who are not eligible for radical treatment typically have a poor overall prognosis. Treatment strategies that can convert unresectable HCC into resectable HCC may improve patient survival. We conducted a single arm phase 2 trial to evaluate the efficacy and safety of Sintilimab plus Lenvatinib as conversion therapy for HCC.
METHODS
A single-arm, single-center study conducted in China (NCT04042805). Adults (≥18 years) with Barcelona Clinic Liver Cancer (BCLC) Stage B or C HCC ineligible for radical surgery with no distant/lymph node metastasis received Sintilimab 200 mg IV on day 1 of a 21-day cycle plus Lenvatinib 12 mg (body weight ≥60 kg) or 8 mg (body weight <60 kg) orally once daily. Resectability was based on imaging and liver function. The primary endpoint was objective response rate (ORR), assessed using RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), event-free survival (EFS) in patients who underwent resection, surgical conversion rate, and safety.
RESULTS
Overall, 36 patients were treated between August 1, 2018, and November 25, 2021; the median age was 58 years (range, 30-79), and 86% were male. The ORR (RECIST v1.1) was 36.1% (95% CI, 20.4-51.8) and the DCR was 94.4% (95% CI, 86.9-99.9). Eleven patients underwent radical surgery and one received radiofrequency ablation and stereotactic body radiotherapy; after a median follow up of 15.9 months, all 12 were alive and four had recurrence, median EFS was not reached. Median PFS among 24 patients who did not undergo surgery was 14.3 months (95% CI, 6.3-26.5). Treatment was generally well tolerated; two patients had serious adverse events; there were no treatment-related deaths.
CONCLUSIONS
Sintilimab plus Lenvatinib is safe and feasible for the conversion treatment of intermediate to locally advanced HCC initially unsuitable for surgical resection.
引言
不符合根治性治疗条件的中期或局部晚期肝细胞癌（HCC）患者总体预后通常较差。能够将不可切除的HCC转化为可切除的HCC的治疗策略可能会提高患者生存率。我们开展了一项单臂2期试验，以评估信迪利单抗联合仑伐替尼作为HCC转化治疗的疗效和安全性。
方法
在中国开展的一项单臂、单中心研究（NCT04042805）。年龄≥18岁、巴塞罗那临床肝癌（BCLC）分期为B期或C期、不符合根治性手术条件且无远处/淋巴结转移的HCC患者，在21天周期的第1天接受200 mg信迪利单抗静脉注射，同时口服仑伐替尼12 mg（体重≥60 kg）或8 mg（体重<60 kg），每日1次。可切除性基于影像学和肝功能评估。主要终点为客观缓解率（ORR），采用RECIST v1.1进行评估。次要终点包括疾病控制率（DCR）、无进展生存期（PFS）、接受手术切除患者的无事件生存期（EFS）、手术转化率和安全性。
结果
总体而言，2018年8月1日至2021年11月25日期间共治疗36例患者；中位年龄为58岁（范围30 - 79岁），86%为男性。ORR（RECIST v1.1）为36.1%（95%CI，20.4 - 51.8），DCR为94.4%（95%CI，86.9 - 99.9）。11例患者接受了根治性手术，1例接受了射频消融和立体定向体部放疗；中位随访15.9个月后，12例患者均存活，4例复发，未达到中位EFS。24例未接受手术患者的中位PFS为14.3个月（95%CI，6.3 - 26.5）。治疗耐受性总体良好；2例患者出现严重不良事件；无治疗相关死亡。
结论
信迪利单抗联合仑伐替尼用于最初不适合手术切除的中期至局部晚期HCC的转化治疗是安全可行的。
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