Sunitinib Versus Sorafenib in Advanced Hepatocellular Cancer: Results of a Randomized Phase III Trial

• Published in: Journal of clinical oncology Vol. 31; no. 32; pp. 4067 - 4075
• Main Authors: CHENG, Ann-Lii, KANG, Yoon-Koo, OMATA, Masao, LOWENTHAL, Susan Pitman, LANZALONE, Silvana, LIQIANG YANG, JOSE LECHUGA, Maria, RAYMOND, Eric, LIN, Deng-Yn, PARK, Joong-Won, KUDO, Masatoshi, SHUKUI QIN, CHUNG, Hyun-Cheol, XIANGQUN SONG, JIANMINGXU, POGGI, Guido
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.11.2013
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - mortality; Disease-Free Survival; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Indoles - therapeutic use; Kaplan-Meier Estimate; Liver Neoplasms - drug therapy; Liver Neoplasms - mortality; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Niacinamide - analogs & derivatives; Niacinamide - therapeutic use; Phenylurea Compounds - therapeutic use; Proportional Hazards Models; Pyrroles - therapeutic use; Tumors; Young Adult; Antineoplastic agent; Phase III trial; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Hepatic disease; Hepatocellular carcinoma; Malignant tumor; Chemotherapy; Randomization; Sunitinib; Treatment; Cancerology; Sorafenib; Digestive diseases; Clinical trial; Advanced stage; Multikinase inhibitor; Antiangiogenic agent; Protein-tyrosine kinase; Comparative study; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2012.45.8372

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