Ann-Lii Cheng1, 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. 1. Ann-Lii Cheng, National Taiwan University Hospital, Taipei; Deng-Yn Lin, Chang Gung Memorial Hospital, Chang Gung University, Guishan Township, Taiwan, Republic of China; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Hyun-Cheol Chung, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul; Joong-Won Park, National Cancer Center, Goyang, Republic of Korea; Masatoshi Kudo, Kinki University Hospital, Osaka; Masao Omata, Yamanashi Prefecture Central Hospital, Kofu, Yamanashi, Japan; Shukui Qin, Nanjing Bayi Hospital, Nanjing; Xiangqun Song, Tumor Hospital of Guangxi Zhuang Autonomous Region, Nanning; Jianming Xu, Beijing 307 Hospital Cancer Centre, Beijing, People's Republic of China; Guido Poggi, Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia; Silvana Lanzalone, Maria Jose Lechuga, Pfizer Italia Srl, Milan, Italy; Susan Pitman Lowenthal, Pfizer Oncology, New York, NY; Liqiang Yang, Pfizer Oncology, La Jolla, CA; Eric Raymond, Service Inter Hospitalier de Cancerologie Bichat-Beaujon, Clichy, France.
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.
RCT Entities:
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-infectedpatients (7.6 v 8.0 months; HR, 1.10; one-sided P = .8286), but was shorter with sunitinib in hepatitis C-infectedpatients (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-infectedpatients. OS was superior in hepatitis C-infectedpatients who received sorafenib. Sunitinib-treated patients reported more frequent and severe toxicity.