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

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Objective:</i></b> We aimed to assess efficacy and tolerability of sequential systemic therapy of advanced HCC. <b><i>Methods:</i></b> 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). <b><i>Results:</i></b> Patients had well-compensated liver function and good performance status at start of each systemic therapy. Agents included sorafenib (<i>n</i> = 14), regorafenib (<i>n</i> = 10), immunotherapy with nivolumab or pembrolizumab (<i>n</i> = 10), lenvatinib (<i>n</i> = 3), ramucirumab (<i>n</i> = 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. <b><i>Conclusions:</i></b> 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.

Characterization of Gut Microbiota and Exploration of Potential Predictive Model for Hepatocellular Carcinoma Microvascular Invasion

“…The risk of recurrence after resection is up to 70% after 5 years, and the 5-year survival rate is as low as 18% (3). Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer (4), and most patients with HCC have metastatic disease or vascular invasion at their initial diagnosis (5)(6)(7). HCC tumors are heterogeneous, and patients at the same disease stage may have very different treatment outcomes (1).…”

New Opportunities in the Systemic Treatment of Hepatocellular Carcinoma—Today and Tomorrow

“…For instance, von Felden et al described 14 patients intolerant or who progressed after sorafenib. These patients were treated with the median of three treatment lines and the median OS from the start of sorafenib was 37.4 months [136]. Moreover, in the previously mentioned RELEVANT study, median OS in the cohort treated sequentially with immunotherapy was 47 months [55].…”

Real-world comparison of pembrolizumab and nivolumab in advanced hepatocellular carcinoma

“…Growing real-world evidence has confirmed the efficacy and safety of nivolumab or pembrolizumab alone for the treatment of advanced HCC [ 20 – 23 ]. However, comparisons between pembrolizumab and nivolumab for the management of pretreated HCC are limited.…”