Subsequent Treatment after Transarterial Chemoembolization Failure/Refractoriness: A Review Based on Published Evidence

Abstract

Transarterial chemoembolization (TACE) is widely applied for the treatment of hepatocellular carcinoma. Repeat TACE is often required in clinical practice because a satisfactory tumor response may not be achieved with a single session. However, repeated TACE procedures can impair liver function and increase treatment-related adverse events, all of which prompted the introduction of the concept of "TACE failure/refractoriness". Mainly based on evidence from two retrospective studies conducted in Japan, sorafenib is recommended as the first choice for subsequent treatment after TACE failure/refractoriness. Several studies have investigated the outcomes of other subsequent treatments, including locoregional, other molecular targeted, anti-programmed death-1/anti-programed death ligand-1 therapies, and combination therapies after TACE failure/refractoriness. In this review, we summarize the up-to-date information about the outcomes of several subsequent treatment modalities after TACE failure/refractoriness.

Role of Transarterial Chemoembolization in the Treatment of Hepatocellular Carcinoma

“…In contrast, a recently published article reviewing the current evidence on subsequent treatment after TACE failure/refractoriness concluded that not only sorafenib, but also other therapies such as TACE with drug-eluting beads, hepatic arterial infusion chemotherapy, ablation, and TACE combined with systemic therapies are potentially useful as subsequent treatment after TACE failure/refractoriness. 47 In addition, a nationwide online survey by the Chinese College of Interventionalists (CCI) in 2020 found an obvious difference in the recognition of TACE failure/refractoriness among Chinese clinicians based on existing definitions. 48 Recently, an expert consensus on TACE refractoriness and subsequent therapies in HCC was published by the CCI.…”

Hepatic arterial infusion chemotherapy combined with lenvatinib and PD‐1 inhibitors versus lenvatinib and PD‐1 inhibitors for HCC refractory to TACE

“…2,6,7 Unfortunately, the efficacy and outcomes of patients receiving systemic therapies alone are still unsatisfactory in clinical practice. 8 Ethical approval: The study was conducted in accordance with the 1964 Declaration of Helsinki and its later amendments and was approved by the Ethics Committee of Jiangsu Cancer Hospital (approval no. 2023-039).…”

“…Hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is a locoregional interventional therapy that can increase local chemotherapeutic drug concentrations to enhance the tumor response rate and reduce systemic toxicity 9,10 and is recommended as one of the first-line options for advanced HCC, especially in patients with portal vein invasion. 11,12 A considerable number of studies have attempted to investigate the efficacy of locoregional treatment with HAIC for HCC when TACE is ineffective or unsuitable, 8,13 while the survival benefits provided by a single HAIC treatment option are also limited and even inferior to those of sorafenib alone. [13][14][15] In recent years, a few studies have demonstrated that combined therapy with HAIC, MTAs, and ICIs has potential therapeutic effects for advanced or TACE-refractory HCC.…”

“…According to the current guidelines, if faced with TACE refractoriness or failure, patients are switched to systemic therapies, including molecular targeted agents (MTAs), immune checkpoint inhibitors (ICIs) or their combinations 2,6,7 . Unfortunately, the efficacy and outcomes of patients receiving systemic therapies alone are still unsatisfactory in clinical practice 8 …”

“…A considerable number of studies have attempted to investigate the efficacy of locoregional treatment with HAIC for HCC when TACE is ineffective or unsuitable, 8,13 while the survival benefits provided by a single HAIC treatment option are also limited and even inferior to those of sorafenib alone 13–15 . In recent years, a few studies have demonstrated that combined therapy with HAIC, MTAs, and ICIs has potential therapeutic effects for advanced or TACE‐refractory HCC 16,17 …”