Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: a single-arm, phase II trial

作者：Wenwen Zhang, Shuang Tong, Bingyang Hu, Tao Wan, Haowen Tang, Feilong Zhao, Tianyu Jiao, Junfeng Li, Ze Zhang, Jinping Cai, Huiyi Ye, Zhanbo Wang, Shiqing Chen, Yafei Wang, Xuerui Li, Fangzhou Wang, Junning Cao, Lantian Tian, Xiaochen Zhao, Mingyi Chen, Hongguang Wang, Shouwang Cai, Minggen Hu, Yuezong Bai, Shichun Lu · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2023 · DOI：10.1136/jitc-2023-007366 · 被引用次数：135 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cancer Immunotherapy and Biomarkers、Cholangiocarcinoma and Gallbladder Cancer Studies

Background Over 70% of the patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage and lose the opportunity for radical surgery. Combination therapy of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death protein-1 (PD-1) antibodies has achieved a high tumor response rate in both the first-line and second-line treatment of advanced HCC. However, few studies have prospectively evaluated whether TKIs plus anti-PD-1 antibodies could convert unresectable intermediate-advanced HCC into resectable disease. Methods This single-arm, phase II study enrolled systemic therapy-naïve adult patients with unresectable Barcelona Clinic Liver Cancer stage B or C HCC. Patients received oral lenvatinib one time per day plus intravenous anti-PD-1 agents every 3 weeks (one cycle). Tumor response and resectability were evaluated before the fourth cycle, then every two cycles. The primary endpoint was conversion success rate by investigator assessment. Secondary endpoints included objective response rate (ORR) by independent imaging review (IIR) assessment per modified RECIST (mRECIST) and Response Evaluation Criteria in Solid Tumors, V.1.1 (RECIST 1.1), progression-free survival (PFS) and 12-month recurrence-free survival (RFS) rate by IIR per mRECIST, R0 resection rate, overall survival (OS), and safety. Biomarkers were assessed as exploratory objectives. Results Of the 56 eligible patients enrolled, 53 (94.6%) had macrovascular invasion, and 16 (28.6%) had ext...