Lenvatinib combined with nivolumab in advanced hepatocellular carcinoma-real-world experience.

Abstract

Lenvatinib, a multi-tyrosine kinase inhibitor that inhibits vascular endothelial growth factor and fibroblast growth factor receptors pathway, activated the immune response in tumor microenvironment. However, the combination of lenvatinib and anti-PD-1 has been reported in early phase studies. Hence, this study aims to explore the efficacy and toxicity of lenvatinib combined with nivolumab in the real-world setting. Advanced HCC patients who underwent lenvatinib combined with nivolumab (L + N group) treatment at Taipei Veterans General Hospital (Taipei, Taiwan) were reviewed between January 2016 and December 2020. Treatment response and outcomes were collected and analyzed. A control group with lenvatinib (L group) was also included for comparison. Forty patients were included in L + N group and 47 in L group. The L + N group demonstrated a higher objective response rate than L group (45.0% vs. 23.4%, p = 0.03). The L + N group also achieved longer PFS (7.5 vs. 4.8 months, p = 0.05) and OS (22.9 vs. 10.3 months, p = 0.01) than L group. Patients with HBV infection and REFLECT criteria fit demonstrated a trend of better prognosis. The PFS for those with PR, SD and PD groups were 11.2, 6.4, and 2.2 months and OS were non-reached, 14.6 and 4.7 months, respectively. Portal vein thrombosis (HR 4.3, 95% C.I. 1.5-12.8) and AFP > 400 ng/mL (HR 3.3, 95% C.I. 1.1-9.3) were poor prognostic factors and nivolumab used remained a protective factor (HR 0.2, 95% C.I. 0.1-0.7). Dermatitis (35.0%), pruritis (27.5%), and hypothyroidism (27.5%) were the common toxicities. Few patients developed grade 3/4 toxicities, including dermatitis (15%), gastrointestinal bleeding (7.5%), hypertension (5.0%), pneumonitis (2.5%) and stomatitis (2.5%). This is the first real-world data reporting the promising efficacy and tolerable toxicities of lenvatinib combined with nivolumab in advanced HCC. Further randomized trials are prompted.

• Authors: Wen-Chi Wu, Tzu-Yuan Lin, Ming-Huang Chen, Yi-Ping Hung, Chien-An Liu, Rheun-Chuan Lee, Yi-Hsiang Huang, Yee Chao, San-Chi Chen
• Journal: Investigational new drugs (Invest New Drugs) Vol. 40 Issue 4 Pg. 789-797 (08 2022) ISSN: 1573-0646 [Electronic] United States
• PMID: 35477812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Antineoplastic Agents
• Phenylurea Compounds
• Quinolines
• Nivolumab
• lenvatinib

Topics

• Antineoplastic Agents (adverse effects, therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Dermatitis (etiology)
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Nivolumab (therapeutic use)
• Phenylurea Compounds (adverse effects, therapeutic use)
• Quinolines (adverse effects, therapeutic use)
• Tumor Microenvironment