Sequential Systemic Treatment in Advanced Hepatocellular Carcinoma Is Able to Prolong Median Survival to More than 3 Years in a Selected Real-World Cohort.

INTRODUCTION

The number of efficacious systemic agents for advanced hepatocellular carcinoma (HCC) has rapidly increased over the past 3 years. However, guidance for optimal sequential systemic treatment in patients with advanced disease and experience with outcome and safety profiles are lacking.

OBJECTIVE

We aimed to assess efficacy and tolerability of sequential systemic therapy of advanced HCC.

METHODS

Our single-center study prospectively followed 14 patients who received multiple, sequential systemic therapies after progression or intolerance to sorafenib. Endpoints were overall and progression-free survival (OS, PFS), objective response rate (ORR), and treatment-emergent adverse events (TEAE).

RESULTS

Patients had well-compensated liver function and good performance status at start of each systemic therapy. Agents included sorafenib ( = 14), regorafenib ( = 10), immunotherapy with nivolumab or pembrolizumab ( = 10), lenvatinib ( = 3), ramucirumab ( = 2), and others, with a median of 3 lines of systemic therapy per patient. Median OS was 37.4 months from initiation of first-line therapy with sorafenib. PFS and ORR for sorafenib, regorafenib, and immunotherapy were 6.6, 5.3, and 6.6 months, and 15.4, 11.1, and 22.2%, respectively. TEAE were frequent (46-80%), but mostly manageable during tyrosine kinase inhibitor therapy and without the need for termination in most patients. However, TEAE due to immunotherapy (60%) led to cessation of treatment in 40% of the patients.

CONCLUSIONS

Sequential systemic therapy is able to prolong median OS in selected patients with advanced HCC to more than 3 years. TEAE are frequent, but manageable, and the quality of adverse events depends on the respective agent. Further investigation of potential predictive biomarkers for treatment allocation is needed.