Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma (HCC): Asia-Pacific (AP) trial subgroup analyses by baseline transaminase (ALT/AST)/α-fetoprotein (AFP) levels

Abstract

4590^ Background: Results of the phase III, randomized, double blind, placebo-controlled AP trial demonstrated that sorafenib is effective and safe for the treatment of advanced HCC in patients from the AP region (Cheng et al, Lancet Oncol, 2009). Hepatic function influences treatment as a measure of organ damage and tumor stage. We performed subset analyses of the AP study dataset according to baseline hepatic function, as indicated by levels of ALT/AST and AFP. Methods: Patients (N=226) with advanced HCC, ECOG PS 0–2, Child-Pugh class A, and no prior systemic therapy were randomized 2:1 to receive sorafenib 400 mg BID or placebo. Endpoints included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for ≥28 days from first demonstration of response), time to progression (TTP) and safety. Patients were grouped by baseline levels of ALT/AST (normal, mild, or moderate) and AFP (normal or abnormal). Results: Median TTP, OS and DCR by subset are shown in the table . The most common grade 3/4 adverse events in the sorafenib populations were hand-foot skin reaction and diarrhea. Conclusions: Sorafenib was effective and safe in patients from the AP region with advanced HCC within a broad range of baseline hepatic enzyme and AFP levels. These results suggest that sorafenib is an effective treatment for HCC, irrespective of baseline ALT/AST or AFP levels. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .