Open AccessSequential Systemic Treatment in Advanced Hepatocellular Carcinoma Is Able to Prolong Median Survival to More than 3 Years in a Selected Real-World Cohort
Author(s) -
Johann von Felden,
Kathrin Karkmann,
Harald Ittrich,
Ines Gil-Ibanez,
Thorben Fründt,
Jenny Krause,
Ansgar W. Lohse,
Henning Wege,
Kornelius Schulze
Publication year - 2020
Publication title -
visceral medicine
Language(s) - English
Resource type - Journals
eISSN - 2297-475X
pISSN - 2297-4725
DOI - 10.1159/000507381
Subject(s) - sorafenib , medicine , regorafenib , tolerability , nivolumab , hepatocellular carcinoma , lenvatinib , ramucirumab , oncology , systemic therapy , adverse effect , pembrolizumab , combination therapy , progression free survival , immunotherapy , gastroenterology , chemotherapy , cancer , colorectal cancer , breast cancer
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 ( n = 14), regorafenib ( n = 10), immunotherapy with nivolumab or pembrolizumab ( n = 10), lenvatinib ( n = 3), ramucirumab ( n = 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.