Lenvatinib Plus Immune Checkpoint Inhibitors Improve Survival in Advanced Hepatocellular Carcinoma: A Retrospective Study

Abstract

BackgroundNivolumab and pembrolizumab disrupt the programmed cell death-1 immune checkpoint and display promising efficacy and safety results in advanced hepatocellular carcinoma (HCC). However, the benefits remain limited. The preliminary results of lenvatinib (LEN) combined with immune checkpoint inhibitors (ICIs) reveal that the combinations were well-tolerated and encouraging. This study aimed to analyze the safety and efficacy of LEN plus ICIs in a real-world cohort of patients with advanced HCC.MethodBetween June 4, 2017, and June 30, 2019, 16 patients received LEN plus nivolumab, and 13 patients were treated with LEN plus pembrolizumab, with the confirmed advanced HCC retrospectively analyzed. The clinical parameters, as well as the outcomes, were assessed.ResultsAll the patients had Barcelona Clinical Liver Cancer Stage C. LEN with ICIs was used as systemic second-, third-, and fourth-line treatments in seven (24.1%), 14 (48.3%), and eight (27.6%) patients, respectively. At the time of data cutoff, six patients (37.5%) were still receiving LEN with nivolumab, while another six patients (46.2%) were still receiving LEN with pembrolizumab. An objective response was recorded in seven patients (25.9%), while the best overall responses were from one complete response and six partial responses. The 6- and 12-month over survival (OS) rates were 62.6% and 53.7%, respectively. Furthermore, the 6- and 12-month progression-free survival (PFS) rates were 43.5% and 31.8%, respectively. In the subgroup analyses, the 6- and 12-month OS and PFS rates for patients treated with LEN plus nivolumab were 62.5% and 52.1%, respectively, and 43.8% and 30.0%, respectively. The 6- and 12-month OS and PFS rates for patients treated with LEN plus pembrolizumab were 51.3% and 51.3%, respectively, and 49.2% and 49.2%, respectively. A total of 11 (31%) deaths were reported in this study, four of which were attributed to grade 5 adverse events presented as fatal treatment-related hepatitis.ConclusionThe combination of LEN and ICIs is a promising new strategy for the treatment of HCC patients. However, high-grade hepatic toxicity was observed and further evaluation of this combination is still required.

Survival of Patients Subjected to Hepatectomy After Spontaneous Rupture of Hepatocellular Carcinoma: A Meta-analysis of High-quality Propensity Score Matching Studies

“…Few studies have focused on the treatment of rHCC survivors, and subsequent treatment strategies are mainly determined clinically based on the tumor burden of rHCC survivors after the recurrence. Targeted therapies combined with immunotherapy have attracted a huge amount of interest in advanced HCC, leading to new strategies for the management of HCC patients ( 39 ). Taken together the real-life experience with systemic therapy in HCC patients confirms the safety of the treatment in patients with advanced HCC stages and even with reduced liver function.…”

Research progress of spontaneous ruptured hepatocellular carcinoma: Systematic review and meta-analysis

“…Few studies have focused on the treatment of rHCC survivors, and the strategies are mainly determined based on the tumor burden after recurrence. Targeted therapies and immunotherapy are increasingly being considered for the management of advanced HCC ( 42 ).…”

Case Report: Radiotherapy Plus Immunotherapy and Lenvatinib for the Treatment of Recurrent Hepatocellular Carcinoma With a Right Atrium and Inferior Vena Cava Tumor Thrombus

“…Two HCC patients with lung metastases treated with lenvatinib plus pembrolizumab showed a good radiologic response and median PFS of > 12 months ( 30 ). The objective response rate of 29 patients receiving ICIs plus lenvatinib was approximately 25.9%, with one patient having a complete response, 6-month OS was 62.6%, 12-month OS was 53.7%, and 6-month PFS rate was 43.5% ( 31 ).…”