Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference

Llovet, Josep M.; Villanueva, Augusto; Marrero, Jorge A.; Schwartz, Myron; Meyer, Tim; Galle, Peter R.; Lencioni, Riccardo; Greten, Tim F.; Kudo, Masatoshi; Mandrekar, Sumithra J.; Zhu, Andrew X.; Finn, Richard S.; Roberts, Lewis R.

doi:10.1002/hep.31327

Cited by 306 publications

(347 citation statements)

References 196 publications

(344 reference statements)

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“…Thus, more work is needed to confirm whether new extrahepatic lesions developed in these second‐line settings are prognostic of PPS outcomes, as well as whether outcomes are similar in biomarker‐defined populations. Stratification for patterns of progression has been considered for trial design in HCC in a recent consensus manuscript 18 …”

Section: Discussionmentioning

confidence: 99%

Pattern of progression in advanced hepatocellular carcinoma treated with ramucirumab

Reig

Galle

Kudo

et al. 2020

Liver International

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Background & Aims Radiological progression patterns to first‐line sorafenib have been associated with post‐progression and overall survival in advanced hepatocellular carcinoma, but these associations remain unknown for therapies in second‐ and later‐line settings. This post hoc analysis of REACH and REACH‐2 examined outcomes by radiological progression patterns in the second‐line setting of patients with advanced hepatocellular carcinoma treated with ramucirumab or placebo. Methods Patients with advanced hepatocellular carcinoma, Child‐Pugh A and Eastern Cooperative Oncology Group Performance Status 0 or 1 with prior sorafenib were randomized to receive ramucirumab 8mg/kg or placebo every 2 weeks. Among 625 patients with ≥1 progression pattern (new extrahepatic lesion [including new macrovascular invasion], new intrahepatic lesion, extrahepatic growth or intrahepatic growth), data were analysed by trial and for pooled individual patient data for REACH‐2 and REACH (alpha‐fetoprotein ≥400 ng/mL). Cox models evaluated prognostic implications of progression patterns on overall and post‐progression survival. Results Post‐progression survival was worse among those with new extrahepatic lesions in REACH (HR 2.33, 95% CI 1.51‐3.60), REACH‐2 (HR 1.49, 95% CI 0.72‐3.08) and the pooled population (HR 1.75, 95% CI 1.12‐2.74) compared to other progression patterns. Overall survival was also significantly reduced in those with new extrahepatic lesions across studies. Ramucirumab provided an overall survival benefit across progression patterns, including patients with new extrahepatic lesions (HR 0.56, 95% CI 0.39‐0.80) in the pooled population. Conclusions The emergence of new extrahepatic lesions in the second‐line setting is a poor prognostic factor for post‐progression survival. The benefit of ramucirumab for overall survival was consistent across progression patterns.

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Section: Discussionmentioning

confidence: 99%

Pattern of progression in advanced hepatocellular carcinoma treated with ramucirumab

Reig

Galle

Kudo

et al. 2020

Liver International

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“…The Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement proposed that the TACE unsuitability should be defined by the following characteristics: (1) unlikely to respond to TACE (confluent multinodular type, massive or infiltrative type, simple nodular type with extranodular growth, poorly differentiated type, intrahepatic multiple disseminated nodules, or sarcomatous changes after TACE); (2) likely to develop TACE failure/refractoriness (exceeding the up-to seven criteria); and, (3) likely to become Child-Pugh B or C after TACE (exceeding the up-to seven criteria and mALBI grade 2b) [76]. The AASLD Consensus Conference showed that locoregional TACE may still be best approach when patients have a low tumor burden and nodules accessible super-selectively [77]. In contrast, upfront systemic therapy may be better for the patients exceeding the up-to seven criteria [77].…”

Section: Exceeding the Up-to Seven Criteria Transcatheter Arterial Cmentioning

confidence: 99%

“…The AASLD Consensus Conference showed that locoregional TACE may still be best approach when patients have a low tumor burden and nodules accessible super-selectively [77]. In contrast, upfront systemic therapy may be better for the patients exceeding the up-to seven criteria [77].…”

Section: Exceeding the Up-to Seven Criteria Transcatheter Arterial Cmentioning

confidence: 99%

Lenvatinib for Hepatocellular Carcinoma: A Literature Review

2021

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Lenvatinib, which is an oral multikinase inhibitor, showed non-inferiority to the sorafenib in terms of overall survival (OS) and a higher objective response rate (ORR) and better progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). A good liver function and Barcelona Clinic Liver Cancer (BCLC) intermediate stage were the key factors in achieving therapeutic efficacy. The management of adverse events plays an important role in continuing lenvatinib treatment. While sequential therapies contributed to prolonging overall survival, effective molecular targeted agents for the administration after lenvatinib have not been established. Repeated transcatheter arterial chemoembolization (TACE) was associated with a decline in the liver function and poor therapeutic response in BCLC intermediate patients. Recently, the Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement proposed the criteria for TACE unsuitability. Upfront systemic therapy may be better for the BCLC intermediate stage HCC patients with a high tumor burden, while selective TACE will be recommended for obtaining a curative response in patients with a low tumor burden. This article reviews the therapeutic response, management of adverse events, post-progression treatment after Lenvatinib, and treatment strategy for BCLC intermediate stage HCC.

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“…Algorithms for systemic treatment for HCC will resemble spiderwebs (Figure 1). For trial design, it will be key to implement a homogeneous set of inclusion criteria and select appropriate endpoints that will capture real drug benefit 15 . Overall survival is the hardest endpoint, but post‐study medications need to be registered and balanced.…”

Section: Figurementioning

confidence: 99%

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

Fonseca

Forner

2020

Liver International

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Increasing alternatives in systemic treatment for hepatocellular carcinoma: Will algorithms be understandable? The treatment of advanced hepatocellular carcinoma (HCC) has rapidly evolved in the last years. Until the demonstration of survival benefit with sorafenib in 2007, no effective treatment was available. The positive results of sorafenib represented a major breakthrough and triggered interest in the evaluation of new agents. After multiple failures, several agents have recently proven benefit, revolutionizing the treatment options and significantly extending survival of advanced HCC. This hopeful scenario has been crowned by the recently published results of the IMBRAVE-150 trial. 1 This trial proved

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Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference

Cited by 306 publications

References 196 publications

Pattern of progression in advanced hepatocellular carcinoma treated with ramucirumab

Pattern of progression in advanced hepatocellular carcinoma treated with ramucirumab

Lenvatinib for Hepatocellular Carcinoma: A Literature Review

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

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