Lenvatinib plus pembrolizumab for systemic therapy-naïve and -experienced unresectable hepatocellular carcinoma

• Published in: Cancer Immunology, Immunotherapy Vol. 71; no. 11; pp. 2631 - 2643
• Main Authors: Wu, Chi-Jung, Lee, Pei-Chang, Hung, Ya-Wen, Lee, Chieh-Ju, Chi, Chen-Ta, Lee, I-Cheng, Hou, Ming-Chih, Huang, Yi-Hsiang
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2022; Springer Nature B.V
• Subjects: Bilirubin; Cancer Research; Disease control; Hepatocellular carcinoma; Immunology; Immunotherapy; Liver cancer; Medicine; Medicine & Public Health; Monoclonal antibodies; Multivariate analysis; Oncology; Original; Original Article; Patients; Pembrolizumab; Solid tumors; Targeted cancer therapy; Systemic therapy; HCC; Immunotherapy; Target therapy; First-line setting
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-022-03185-6

Background Lenvatinib combined with pembrolizumab showed a promising result in an early phase study for hepatocellular carcinoma (HCC). The efficacy and safety of lenvatinib plus pembrolizumab for patients with unresectable HCC (uHCC) beyond the first-line setting were unclear. Methods Seventy-one consecutive patients who received lenvatinib plus pembrolizumab for uHCC were prospectively enrolled. Effect of lenvatinib combinations on Albumin-Bilirubin (ALBI) score and factors associated with progression-free survival (PFS) and overall survival (OS) were analyzed. Results Of the 71 cases, 58 (81.7%) were in BCLC C. There were 44 (62%) for the first-line systemic treatment, and 27 (38%) had experienced targeted therapy or nivolumab treatment. The objective response rate and disease control rate (DCR) were 34.1% and 84.1% for the first-line setting, and 18.5% and 70.4% for systemic therapy-experienced cases (Response Evaluation Criteria in Solid Tumors version 1.1, RECIST v1.1), respectively. The mean ALBI score was stable during the treatment course. After a median of 9.3 months of follow-up, the median PFS was 9.3 months versus 4.4 months, and the median OS was not estimable yet versus 12 months for Child–Pugh A versus B patients, respectively. Prior nivolumab failure was the only significant factor associated with poorer PFS (HR = 3.253, p  = 0.004). Child–Pugh class B (HR = 2.646, p  = 0.039) and prior nivolumab failure (HR = 3.340, p  = 0.014) were independent factors for poorer OS in multivariate analysis. Conclusions A high DCR was observed by lenvatinib/pembrolizumab combination without adverse effect on ALBI score for systemic therapy-naïve and -experienced uHCC. Suboptimal response to prior nivolumab-failed patients requires further exploration .