Asia-Pacific Primary Liver Cancer Expert Research Articles

Risk of Variceal Bleeding in Patients With Advanced Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab

Risk of Variceal Bleeding in Patients With Advanced Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab

The 12th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2022)

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REPLACEMENT trial in progress: Combination therapy with atezolizumab plus bevacizumab for TACE unsuitable patients with beyond up-to-seven criteria in intermediate stage hepatocellular carcinoma: A phase II study.

TPS4162 Background: Transarterial chemoembolization (TACE) had been developed as a standard of care in patients with intermediate-stage HCC at a time when systemic therapy was not available. This stage includes a certain TACE-unsuitable subpopulation, such as beyond up-to-seven criteria. Recently, the American Association for the Study of Liver Diseases and Asia-Pacific Primary Liver Cancer Expert Meeting have recommended systemic therapy for those patients to achieve overall survival (OS) beyond 2 years without impaired liver function in their consensus guideline. However, there is not enough data on systemic therapy for this population. Atezolizumab (Atezo), anti-PD-L1 antibody, plus Bevacizumab (Bev), anti-VEGF antibody, combination therapy has been shown to significantly improve OS, progression-free survival (PFS), and overall response rate (ORR) against sorafenib, which is a standard of care in unresectable HCC according to a phase III randomized controlled trial, IMbrave150. Therefore, we investigate the efficacy and safety of Atezo+Bev combination therapy in patients with HCC beyond up-to-seven criteria in this trial. Methods: REPLACEMENT trial is a multicenter, single-arm phase II study of Atezo+Bev combination therapy. Key eligibility criteria are age ≥20 years, ECOG performance status 0-1, Child-Pugh A, no vascular invasion, no extrahepatic metastasis, beyond up-to-seven criteria, and patients who have received neither systemic therapy nor TACE. Patients will be administrated Atezo 1200 mg/body + Bev 15 mg/kg once every 3 weeks. The primary endpoint is PFS per modified RECIST (mRECIST). The secondary endpoints include PFS, ORR, duration of response (DOR) per mRECIST; PFS, ORR, DOR per RECIST ver.1.1; OS and safety including change of liver function based on albumin-bilirubin (ALBI) score until disease progression. A total of 60 events are necessary to investigate the hypothesis that a target point estimation of PFS rate at 6 months (null population: 55%, alternative population: 73%). The estimated sample size is, therefore, 70 patients. In addition, the results of the Atezo+Bev therapy in this arm will be compared with those in approximately 600 TACE treated consecutive patients with intermediate-stage HCC, using the propensity score matching method, as an exploratory analysis of a possible replacement of TACE by the Atezo+Bev therapy. Patients’ enrollment had already started in December 2020, and 12 patients were enrolled as of 16th February ’21. Clinical trial information: jRCTs071200051.

Lenvatinib for Hepatocellular Carcinoma: A Literature Review.

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.

Treatment Strategy of Transarterial Chemoembolization for Hepatocellular Carcinoma

Transarterial chemoembolization (TACE) is a first-line treatment for patients with hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer stage B (BCLC-B). There are two major techniques of TACE: conventional TACE (cTACE) using iodized oil and gelatin sponge particles, and TACE using drug-eluting beads (DEB-TACE). The latest randomized controlled trial proved the superiority of cTACE regarding local effects over DEB-TACE; however, cTACE also damages the liver more severely. Therefore, cTACE should be performed for localized HCCs as selectively as possible. On the other hand, DEB-TACE has less liver toxicity and is favorable for patients with an advanced age, large and/or bilobar tumors, or a poor liver function. However, some BCLC-B HCCs are TACE-resistant and the concept of TACE unsuitability (mainly up-to-7 criteria out) has been proposed by Asia-Pacific Primary Liver Cancer Expert Meeting. Systemic therapy is recommended for patients with TACE-unsuitable HCC; however, the condition of TACE-unsuitable HCC does not always rule out TACE monotherapy and some up-to-7 criteria out tumors may also be good candidates for superselective cTACE when localized in limited liver segments. The sequential therapy of an antiangiogenic and TACE is also a novel option for patients with TACE-unsuitable HCC, antiangiogenic-refractory HCC, or even down-staged HCC.

The 10th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2019), Sapporo, Japan, August 29-31, 2019

The 10th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2019), Sapporo, Japan, August 29-31, 2019

A review of updated guidelines for radiotherapy for primary liver cancer

The treatment guidelines based on evidence-based medical evidence provide appropriate treatment strategies for clinical oncologists. Currently, many treatment guidelines for primary liver cancer have been published and updated by many organizations from different countries, including Barcelona Clinic Liver Cancer (BCLC), European Association for the Study of the Liver and European Organization for Research and Treatment of Cancer (EASL-EORTC), American Association for the Study of Liver Diseases (AASLD), National Comprehensive Cancer Network (NCCN), Asia-Pacific Primary Liver Cancer Expert (APPLE), Korean Liver Cancer Study Group and National Cancer Center (KLCSG-NCC), and Chinese Society for Therapeutic Radiology and Oncology (CSTRO), Chinese Medical Association. Although radiotherapy is commonly used in clinical practice, some guidelines do not accept it as a standard treatment strategy. In this article, we review the current treatment guidelines and discuss the current status and future prospects of radiotherapy in the management of primary liver cancer. Key words: Liver neoplasms/radiotherapy; Consensus

Selected summary for the 2015 Asia–Pacific Primary Liver Cancer Expert Meeting (APPLE)

Liver cancer is now ranked second in terms of cancer-related mortality worldwide; with limited treatment options for patients at advanced stages it remains a growing health problem. All Phase III clinical trials testing molecular therapies after sorafenib have so far failed, and there is still not a validated oncogene addiction loop. Despite the present huge challenges, advancements in the recent years have been remarkable. The Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE) was designed to promote scientific exchanges of international and regional experts in the study and management of liver cancer. Over the years it has consolidated as a major resource to provide a thorough update to clinicians and researchers located in the Asia-Pacific region in different aspects of liver cancer. Attendance at these meetings is exceptional, with an average of 1000 attendees at each conference. As predicted, the 2015 edition provided an outstanding overview of the latest developments in the clinical management and molecular pathogenesis of the disease.