The calm before the storm: a report from the International Liver Cancer Association Congress 2015 – part 2
International Liver Cancer Association Congress 2015, Paris, France, 4–6 September 2015 Since its creation 9 years ago, in 2007, the International Liver Cancer Association has focused on the multidisciplinary approach to liver cancer due to advances in hepatology science and care worldwide. In its 2015 annual conference, held on 4–6 September in Paris, France, the most recent progresses in the basic biology, management and treatment of liver cancer have been presented. This report, divided into two parts, introduces and critically reviews some of the most intriguing topics discussed at the meeting.
Systemic therapy for intermediate and advanced hepatocellular carcinoma: Sorafenib and beyond.
The hepatocellular carcinoma (HCC) treatment landscape changed a decade ago, with sorafenib demonstrating survival benefit in the first-line setting and becoming the first systemic therapy to be approved for HCC. More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib, with further positive phase 3 studies emerging in the first line (lenvatinib non-inferior to sorafenib) and second line versus placebo (cabozantinib and ramucirumab). A key recommendation in the management of patients receiving sorafenib is to promote close communication between the patient and the physician so that adverse events (AEs) are detected early and severe AEs can b…
Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation
Regorafenib is one option for second-line treatment of hepatocellular carcinoma (HCC), improving overall survival (OS) of sorafenib-tolerant patients who develop progression. We aim to evaluate the safety and outcomes of regorafenib as second-line treatment for HCC recurrence after liver transplantation (LT). This is a retrospective, multicenter, international study including regorafenib-treated LT patients (2015-2018), with analysis of baseline characteristics and evolutionary events during sorafenib/regorafenib treatment. Twenty-eight LT patients (57 years, 7% cirrhotics, 54% performance status 1) were included. Median time from LT to regorafenib initiation was 3.9 (1.1-18.5) years; media…
Assessing the impact of COVID-19 on liver cancer management (CERO-19)
[Background & Aims] The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic.
Reliability of extracellular contrast versus gadoxetic acid in assessing small liver lesions using liver imaging reporting and data system v.2018 and European association for the study of the liver criteria.
Background & aims: The diagnostic accuracy of Liver Imaging Reporting and Data System (LI-RADS) v.2018 and European Association for the Study of the Liver (EASL) criteria for the diagnosis of HCC have been widely evaluated, but their reliability should be investigated. We aimed to assess and compare the reliability of LI-RADS v.2018 and EASL criteria for the diagnosis of HCC using MRI with extracellular contrast agents (ECAs) and gadoxetic acid (GA) and determine the effect of ancillary features on LI-RADS reliability. Approach & results: Ten readers reviewed MRI studies of 92 focal liver lesions measuring <3 cm acquired with ECAs and GA <1 month apart from two prospective tri…
First-Line Immune Checkpoint Inhibitor-Based Sequential Therapies for Advanced Hepatocellular Carcinoma: Rationale for Future Trials
<b><i>Introduction:</i></b> Atezolizumab (ATEZO) plus bevacizumab (BEVA) represents the new standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the second-line treatment after the failure of immunotherapy-based first-line remains elusive. Taking into account the weaknesses of the available evidence, we developed a simulation model based on available phase III randomized clinical trials (RCTs) to identify optimal risk/benefit sequential strategies. <b><i>Methods:</i></b> A Markov model was built to estimate the overall survival (OS) of sequential first- and second-line systemic treatments. Seque…
Antiviral therapy in the palliative setting of HCC (BCLC-B and -C)
The potential impact of direct-acting antivirals (DAAs) in patients with Barcelona Clinic Liver Cancer (BCLC)-B/C stage hepatocellular carcinoma (HCC) is understudied. Patients with HCC have been systematically excluded from randomised controlled trials evaluating the effectiveness of DAAs. Thus, the benefits of DAAs in patients with HCC are less well defined. The presence of active HCC before the initiation of DAA treatment is reported to be a predictor of DAA failure, and studies in patients without HCC have demonstrated that improvements in cirrhosis complications were lower or absent after DAA failure. Even if viral eradication is achieved using DAAs, reversal of liver function impairme…
Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: An individual patient data meta-analysis
ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk fac…
Regorafenib Efficacy After Sorafenib in Patients With Recurrent Hepatocellular Carcinoma After Liver Transplantation:A Retrospective Study
Background and aim Safety of regorafenib in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been recently demonstrated. We aimed to assess the survival benefit of regorafenib compared to best supportive care (BSC) in LT-patients after sorafenib discontinuation. Methods This observational multicenter retrospective study included LT-patients with HCC-recurrence who discontinued first-line sorafenib. Group-1 was constituted by regorafenib-treated patients, while control group was selected among patients treated with best supportive care (BSC) due to unavailability of second-line options at the time of sorafenib discontinuation and who were sorafenib-tolerant prog…
Tratamiento del carcinoma hepatocelular en España. Análisis de 705 casos en 62 centros
Resumen Fundamento y objetivo El carcinoma hepatocelular (CHC) es la principal causa de muerte en pacientes con cirrosis, y su situacion actual en Espana no es bien conocida. Por esto, se ha creado un registro nacional para evaluar las caracteristicas de los pacientes con CHC de novo. Pacientes y metodo Entre el 1 de octubre de 2008 y el 31 de enero de 2009, 62 centros de referencia registraron las caracteristicas demograficas, clinicas y tumorales, la primera opcion de tratamiento y la elegibilidad para el trasplante ortotopico hepatico (TOH) de los CHC diagnosticados en este tiempo. Resultados Se contabilizaron 705 casos nuevos de CHC, un 78% en varones; la edad media era de 65 anos y un …
International and multicenter real‐world study of sorafenib‐treated patients with hepatocellular carcinoma under dialysis
Background & Aims: Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population. Methods: We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded. Results: As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dial…
HCC surveillance improves early detection, curative treatment receipt, and survival in patients with cirrhosis: A meta-analysis
Background & Aims: There is controversy regarding the overall value of hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis given the lack of data from randomized-controlled trials. To address this issue, we conducted a systematic review and meta-analysis of cohort studies evaluating the benefits and harms of HCC surveillance in patients with cirrhosis. Methods: We performed a search of the Medline and EMBASE databases and national meeting abstracts from January 2014 through July 2020 for studies reporting early-stage HCC detection, curative treatment receipt, or overall survival, stratified by HCC surveillance status, among patients with cirrhosis. Pooled risk ratios …
The calm before the storm: a report from the International Liver Cancer Association Congress 2015 – part 1
International Liver Cancer Association Congress 2015, Paris, France, 4–6 September 2015 Since its creation 9 years ago, in 2007, the International Liver Cancer Association has focused on the multidisciplinary approach to liver cancer due to advances in hepatology science and care worldwide. In its 2015 annual conference, held on 4–6 September in Paris, France, the most recent progresses in the basic biology, management and treatment of liver cancer have been presented. This report, divided into two parts, introduces and critically reviews some of the most intriguing topics discussed at the meeting.
Progression-Free Survival Early Assessment Is a Robust Surrogate Endpoint of Overall Survival in Immunotherapy Trials of Hepatocellular Carcinoma
Background: Radiology-based outcomes, such as progression-free survival (PFS) and objective response rate (ORR), are used as surrogate endpoints in oncology trials. We aimed to assess the surrogacy relationship of PFS with overall survival (OS) in clinical trials of systemic therapies targeting advanced hepatocellular carcinoma (HCC) by novel meta-regression methods. Methods: A search of databases (PubMed, American Society of Clinical Oncology (ASCO), and European Society for Medical Oncology (ESMO) Meeting Libraries, Clinicaltrials.gov) for trials of systemic therapies for advanced HCC reporting both OS and PFS was performed. Individual patient data were extracted from PFS and OS Kaplan&nd…
Pattern of progression in advanced hepatocellular carcinoma treated with ramucirumab
Abstract 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 place…