Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial.

Abstract

PURPOSE:

Open-label, phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer.

PATIENTS AND METHODS:

Patients were stratified and randomly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day. Primary end point was overall survival (OS).

RESULTS:

Early trial termination occurred for futility and safety reasons. A total of 1,074 patients were randomly assigned to the study (sunitinib arm, n = 530; sorafenib arm, n = 544). For sunitinib and sorafenib, respectively, median OS was 7.9 versus 10.2 months (hazard ratio [HR], 1.30; one-sided P = .9990; two-sided P = .0014); median progression-free survival (PFS; 3.6 v 3.0 months; HR, 1.13; one-sided P = .8785; two-sided P = .2286) and time to progression (TTP; 4.1 v 3.8 months; HR, 1.13; one-sided P = .8312; two-sided P = .3082) were comparable. Median OS was similar among Asian (7.7 v 8.8 months; HR, 1.21; one-sided P = .9829) and hepatitis B-infected patients (7.6 v 8.0 months; HR, 1.10; one-sided P = .8286), but was shorter with sunitinib in hepatitis C-infected patients (9.2 v 17.6 months; HR, 1.52; one-sided P = .9835). Sunitinib was associated with more frequent and severe adverse events (AEs) than sorafenib. Common grade 3/4 AEs were thrombocytopenia (29.7%) and neutropenia (25.7%) for sunitinib; hand-foot syndrome (21.2%) for sorafenib. Discontinuations owing to AEs were similar (sunitinib, 13.3%; sorafenib, 12.7%).

CONCLUSION:

OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib. OS was comparable in Asian and hepatitis B-infected patients. OS was superior in hepatitis C-infected patients who received sorafenib. Sunitinib-treated patients reported more frequent and severe toxicity.

• Authors: Ann-Lii Cheng, Yoon-Koo Kang, Deng-Yn Lin, Joong-Won Park, Masatoshi Kudo, Shukui Qin, Hyun-Cheol Chung, Xiangqun Song, Jianming Xu, Guido Poggi, Masao Omata, Susan Pitman Lowenthal, Silvana Lanzalone, Liqiang Yang, Maria Jose Lechuga, Eric Raymond
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 31 Issue 32 Pg. 4067-75 (Nov 10 2013) ISSN: 1527-7755 [Electronic] United States
• PMID: 24081937 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Indoles
• Phenylurea Compounds
• Pyrroles
• Niacinamide
• Sorafenib
• Sunitinib

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, mortality)
• Disease-Free Survival
• Female
• Humans
• Indoles (therapeutic use)
• Kaplan-Meier Estimate
• Liver Neoplasms (drug therapy, mortality)
• Male
• Middle Aged
• Niacinamide (analogs & derivatives, therapeutic use)
• Phenylurea Compounds (therapeutic use)
• Proportional Hazards Models
• Pyrroles (therapeutic use)
• Sorafenib
• Sunitinib
• Young Adult