The Combining of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors as First-Line Treatment for Advanced Stage Hepatocellular Carcinoma

J Clin Med. 2022 Aug 19;11(16):4874. doi: 10.3390/jcm11164874.

Abstract

Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers. Tyrosine kinase inhibitors (TKIs), including sorafenib (SOR) and lenvatinib (LEN), as well as immune checkpoint inhibitors (ICIs), including nivolumab (NIVO) and pembrolizumab (PEMBRO), have been approved for the treatment of advanced HCC. The aim of the study is to determine whether advanced-stage HCC patients should receive a combination of TKI and ICI as first-line therapy.

Methods: Data for subjects with BCLC stage C HCC, who were receiving combining TKI and ICI as first-line therapy at Taichung Veterans General Hospital from April 2019 to July 2021, were evaluated. The general and therapeutic outcome data were collected and analyzed.

Results: A total of 33 patients were enrolled (8 SOR/NIVO, 4 SOR/PEMBRO, 11 LEN/NIVO, and 10 LEN/PEMBRO). All cases belonged to Child-Pugh class A. The objective response rate was 48.5%, and disease control rate was 72.7%. The average progression-free survival (PFS) and overall survival (OS) of all patients was 9.2 and 17.0 months, respectively. The use of PEMBRO, when compared with NIVO, had a significantly positive impact towards achieving an objective response, defined as either complete response or partial response (OR 5.54, p = 0.045). PFS and OS between the different TKIs or ICIs had no differences. The most adverse event was fatigue (36.4%), and most cases were mild and manageable.

Conclusion: Combining TKI and ICI provides an acceptable antitumor efficacy in first-line therapy for advanced-stage HCC patients. The survival outcomes between different TKIs or ICIs display no differences.

Keywords: hepatocellular carcinoma; immune checkpoint inhibitor; tyrosine kinase inhibitor.

Grants and funding

This research received no external funding.