Sequential systemic treatment in advanced hepatocellular carcinoma is able to prolong median survival to more than three years

Background and aims:

The number of efficacious systemic agents for advanced hepatocellular carcinoma (HCC) has rapidly increased over the past two years. However, guidance for optimal sequential systemic treatment in patients with advanced disease and experience with outcome and safety profiles are lacking. Thus, we aimed to assess efficacy and tolerability of sequential systemic therapy of HCC.

Patients and methods:

Our single-center study included all patients who received multiple, sequential systemic therapies after progression or intolerance to Sorafenib (start of 2^nd line between Sept 2016 and Oct 2018). Endpoints were overall and progression-free survival (OS, PFS), objective response rate (ORR), and treatment emergent adverse events (TEAE).

Results:

14 patients were identified and prospectively followed. All of them had well compensated liver function and good performance status at start of each systemic therapy. Agents included sorafenib (n = 14), regorafenib (n = 10), immunotherapy with nivolumab or pembrolizumab (n = 10), lenvatinib (n = 3), ramucirumab (n = 2), and others, with a median of three lines of systemic therapy per patient. Median OS was 37.4 months from initiation of 1^st line therapy with sorafenib. PFS and ORR for sorafenib, regorafenib (TKI), 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 TKI therapy without the need for termination. However, TEAEs due to immunotherapy (60%) led to cessation of treatment in 40% of patients.

Fig. 1: Timeline of sequential systemic therapies

Conclusion:

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