American Association for Cancer Research
ccr-23-0060_table_s3_suppts3.pdf (65.52 kB)

Table S3 from Lenvatinib, Toripalimab plus FOLFOX Chemotherapy in Hepatocellular Carcinoma Patients with Extrahepatic Metastasis: A Biomolecular Exploratory, Phase II Trial (LTSC)

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journal contribution
posted on 2023-12-15, 08:42 authored by MinKe He, YeXing Huang, ZeFeng Du, ZhiCheng Lai, Hanyue Ouyang, JingXian Shen, DongSheng Wen, QiJiong Li, YaoJun Zhang, Wei Wei, MinShan Chen, Li Xu, Anna Kan, Ming Shi

Tumor Response


National Natural Science Foundation of China (NSFC)

China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)

Special Project for Research and Development in Key areas of Guangdong Province (广东省科技计划重点领域研发项目)



To investigate the efficacy, safety, and biomarkers of systemic chemotherapy with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) in combination with lenvatinib and toripalimab as the first-line treatment for advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis. In this biomolecular exploratory, phase II trial, eligible patients underwent the triple combination therapy of lenvatinib, toripalimab, plus FOLFOX chemotherapy. Primary endpoint was progression-free survival (PFS) rate at 6 months by RECIST v1.1. Single-nucleus RNA sequencing (snRNA-seq) of tumor biopsy samples was performed for exploratory biomarker analyses. Between November 19, 2019, and July 4, 2021, 30 patients were enrolled. The primary endpoint was a 6-month PFS rate of 66.7%, with a median PFS of 9.73 months [95% confidence interval (CI), 2.89–16.58]. The median overall survival (OS) was 14.63 months (95% CI, 11.77–17.50), with an objective response rate of 43.3%. Twenty-four (80.0%) patients exhibited high-risk features, among whom the median OS and PFS were 13.7 months (95% CI, 9.24–18.16) and 8.3 months (95% CI, 3.02–13.58), respectively. The most common adverse events were neutropenia, and increased aspartate aminotransferase and alanine aminotransferase levels. Exploratory analyses of snRNA-seq profiles suggested that patients with higher abundance of tumor-infiltrating immune cells were more likely to benefit from this combination. In addition, two subtypes of hepatocytes (AKR1C2+ and CFHR4+ malignant hepatocytes) were associated with reduced clinical benefits. FOLFOX chemotherapy in combination with lenvatinib and toripalimab showed promising antitumor activity with manageable toxicities in advanced HCC with extrahepatic metastasis. AKR1C2+ and CFHR4+ hepatocyte subtypes may be predictive biomarkers of resistance to the combination therapy.