Navigating the new landscape of second‐line treatment in advanced hepatocellular carcinoma

Abstract

Sorafenib and lenvatinib are approved for first-line treatment of patients with advanced hepatocellular carcinoma (HCC), and the efficacy of atezolizumab plus bevacizumab has been demonstrated versus sorafenib. Over time, first-line treatment frequently fails, and regorafenib, cabozantinib, ramucirumab (for patients with alpha fetoprotein ≥400 ng/mL), nivolumab, pembrolizumab and ipilimumab plus nivolumab are approved for use after sorafenib (but not lenvatinib) treatment in advanced HCC. Given the considerable complexity in the therapeutic landscape, the objective of this review was to summarize the clinical evidence for second-line agents and provide practical guidance for selecting the best sequential treatment approach. The timing and sequencing of treatment switches are key to optimizing patient outcomes in advanced HCC, and decisions should be informed by reasons for discontinuation of previous therapy and disease progression. It is important not to switch too soon, because sequential treatment benefit may then be lost, nor should switching be delayed too long. Effectiveness, safety and tolerability, patient quality of life, route of administration, dosing regimen, drug class, molecular target and individual patients' characteristics, including comorbidities, inform the selection of second-line systemic treatment, independently of the aetiology of HCC, tumour stage and the response to previous treatment. Biomarkers predictive of treatment effectiveness are of great value, but currently biomarker-driven patient selection is possible only in the case of ramucirumab. The approval of new combination therapies for advanced HCC in the first-line setting will further increase the complexity of decision-making. However, the important factors will remain the individual patient's characteristics and preferences.

<p>ISL Induces Apoptosis and Autophagy in Hepatocellular Carcinoma via Downregulation of PI3K/AKT/mTOR Pathway in vivo and in vitro</p>

“…Although sorafenib and other immunosuppressants have the potential to improve prognosis, the two–five-month survival rate is still poor, which is far lower than that achieved for many other solid tumor types. 30 , 31 Therefore, there is an urgent need to find novel effective drugs for the treatment of HCC. Numerous natural bioactive compounds have attracted interest as complementary and alternative medicines as well as for cancer chemoprevention because of their fewer adverse reactions and some special therapeutic effects.…”

Increasing alternatives in systemic treatment for hepatocellular carcinoma: Will algorithms be understandable?

“…and Wörns discuss the complexity of second-line systemic therapies landscape for HCC. 3 After sorafenib-based therapy, cabozantinib, regorafenib and ramucirumab improved patients outcomes in well-designed phase III trials. [4][5][6] However, it is not yet defined whether these agents perform the same after lenvatinib, which was proven to be non-inferior to sorafenib and is largely available.…”

“…Alejandro Forner 2,3 F I G U R E 1 Proposed algorithm based on published phase III trials and subanalysis of the pivotal agents used for advanced hepatocellular carcinoma. AFP, alpha-foetoprotein; CP, Child-Pugh; ECOG-PS, Eastern Cooperative Oncology Group performance status; IO, immunooncology; miRNA, micro-RNAs; PVT, portal vein thrombosis.…”

“…Within this context, in this issue of Liver International, Rimassa and Wörns discuss the complexity of second‐line systemic therapies landscape for HCC 3 . After sorafenib‐based therapy, cabozantinib, regorafenib and ramucirumab improved patients outcomes in well‐designed phase III trials 4‐6 .…”

Novel Therapies for Hepatocellular Carcinoma

“…In this rapidly evolving scenario, it is extremely important that physicians are updated and aware of novel therapeutic options in order to make the best use of them in various clinical settings [ 19 , 20 ].…”