Efficacy and safety of sorafenib (Sor) in patients (Pts) with advanced hepatocellular carcinoma (HCC): Subgroup analyses of the SHARP trial by baseline (BL) transaminase (ALT/AST)/α-fetoprotein (AFP) and bilirubin (bil) levels.

Abstract

4051^ Background: Results of the phase III, double-blind, placebo (Pla)-controlled SHARP trial demonstrated that Sor is effective and safe for the treatment of advanced HCC. As hepatic function influences treatment options, we examined the effect of Sor on hepatic function, as indicated by bil levels, and performed subset analyses of SHARP according to BL levels of ALT/AST/AFP. Methods: Pts (N=602) were randomized 1:1 to receive Sor 400 mg bid or Pla in 6-week cycles. 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. Pts were grouped by BL levels of ALT/AST (normal, mild, or moderate) and AFP (normal or abnormal). Bil was measured at BL and day 1 of each cycle. Results: TTP, OS, and DCR are shown. No notable differences in the safety profiles were observed between Pts with normal vs elevated ALT/AST/AFP levels. Mean BL levels of bil in the Sor and Pla groups were 0.83 and 0.88 mg/dL, respectively. A transient elevation in bil was observed in Sor pts at cycle 2. Mean change in bil at last cycle in the Sor and Pla groups were 1.01 and 0.95 mg/dL, respectively. Conclusions: These results suggest that Sor is an effective treatment for HCC, irrespective of ALT/AST/AFP levels, and that hepatic function (bil levels) is not appreciably affected by Sor treatment. BL pop Sor (n) Pla (n) Median TTP (Sor/Pla) (mo) TTP HR (95% CI) Median OS (Sor/Pla) (mo) OS HR (95% CI) DCR (%) (Sor/Pla) Total 299 303 5.5/2.8 0.58 (0.45, 0.74) 10.7/7.9 0.69 (0.55, 0.87) 43/32 Normal ALT/AST (<1.8 × ULN) 152 153 5.7/3.9 0.57 (0.41, 0.80) 11.6/8.8 0.68 (0.49, 0.93) 53/39 Mildly elevated ALT/AST (1.8-3.0 × ULN) 77 78 5.3/2.8 0.64 (0.39, 1.04) 9.5/8.5 0.81 (0.53, 1.24) 36/28 Moderately elevated ALT/AST (>3.0 × ULN) 68 72 5.8/2.6 0.54 (0.31, 0.94 6.3/4.6 0.71 (0.46, 1.09) 32/21 Normal AFP (≤ULN) 111 97 9.6/4.1 0.72 (0.46, 1.11) 12.4/9.5 0.76 (0.51, 1.13) 48/41 Elevated AFP (>ULN) 171 194 5.3/2.7 0.55 (0.40, 0.75) 9.4/7.0 0.72 (0.55, 0.95) 40/26 Abbreviation: ULN, upper limit of normal. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, Bayer Schering Pharma Bayer, Novartis Bayer Bayer, Biocompatibles International, Bristol-Myers Squibb, Gilead, Roche, Schering-Plough Bayer 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 2010 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.