Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma:
results of a randomized phase III trial.
Author(s): Cainap C(1), Qin S(2), Huang WT(2), Chung IJ(2), Pan H(2), Cheng Y(2), Kudo M(2),
Kang YK(2), Chen PJ(2), Toh HC(2), Gorbunova V(2), Eskens FA(2), Qian J(2), McKee
MD(2), Ricker JL(2), Carlson DM(2), El-Nowiem S(2).
Affiliation(s): Author information:
(1)Calin Cainap, Institute of Oncology, Cluj-Napoca, Romania; Shukui Qin, Chinese
People's Liberation Army Cancer Center, Bayi Hospital, Beijing; Hongming Pan, Sir
Run Run Shaw Hospital, Zhejiang University, Hangzhou; Ying Cheng, Tumor Hospital
of Jilin Province, Changchun, People's Republic of China; Wen-Tsung Huang, Chi
Mei Medical Center, Liouying; Pei-Jer Chen, National Taiwan University Hospital,
Taipei, Taiwan, Republic of China; Ik Joo Chung, Chonnam National University,
Hwasun Hospital, Hwasun, Jeollonam-do; Yoon-Koo Kang, Asan Medical Center,
University of Ulsan, Seoul, Republic of Korea; Masatoshi Kudo, Kinki University,
Osaka, Japan; Han-Chong Toh, National Cancer Centre, Singapore, Singapore; Vera
Gorbunova, Russian Academy of Medical Sciences, Moscow, Russia; Ferry A.L.M.
Eskens, Cancer Institute, Erasmus University Medical Center, Rotterdam, the
Netherlands; Jiang Qian, Mark D. McKee, Justin L. Ricker, Dawn M. Carlson,
AbbVie, North Chicago, IL; Saied El-Nowiem, Alexandria University, Alexandria,
Egypt. calincainap@yahoo.co.uk. (2)Calin Cainap, Institute of Oncology,
Cluj-Napoca, Romania; Shukui Qin, Chinese People's Liberation Army Cancer Center,
Bayi Hospital, Beijing; Hongming Pan, Sir Run Run Shaw Hospital, Zhejiang
University, Hangzhou; Ying Cheng, Tumor Hospital of Jilin Province, Changchun,
People's Republic of China; Wen-Tsung Huang, Chi Mei Medical Center, Liouying;
Pei-Jer Chen, National Taiwan University Hospital, Taipei, Taiwan, Republic of
China; Ik Joo Chung, Chonnam National University, Hwasun Hospital, Hwasun,
Jeollonam-do; Yoon-Koo Kang, Asan Medical Center, University of Ulsan, Seoul,
Republic of Korea; Masatoshi Kudo, Kinki University, Osaka, Japan; Han-Chong Toh,
National Cancer Centre, Singapore, Singapore; Vera Gorbunova, Russian Academy of
Medical Sciences, Moscow, Russia; Ferry A.L.M. Eskens, Cancer Institute, Erasmus
University Medical Center, Rotterdam, the Netherlands; Jiang Qian, Mark D. McKee,
Justin L. Ricker, Dawn M. Carlson, AbbVie, North Chicago, IL; Saied El-Nowiem,
Alexandria University, Alexandria, Egypt.
Publication date & source: 2015, J Clin Oncol. , 33(2):172-9
PURPOSE: This open-label phase III trial evaluated efficacy and tolerability of
linifanib versus sorafenib in patients with advanced hepatocellular carcinoma
(HCC) without prior systemic therapy.
PATIENTS AND METHODS: Patients were randomly assigned in a 1:1 ratio to linifanib
17.5 mg once daily or sorafenib 400 mg twice daily. Patients were stratified by
region (Outside Asia, Japan, and rest of Asia), Eastern Cooperative Oncology
Group performance score (ECOG PS; 0 or 1), vascular invasion or extrahepatic
spread (yes or no), and hepatitis B virus (HBV) infection (yes or no). The
primary end point of the study was overall survival (OS). Secondary end points
were time to progression (TTP) and objective response rate (ORR) per RECIST v1.1.
RESULTS: We randomly assigned 1,035 patients (median age, 60 years; Asian, 66.6%;
ECOG PS 0, 65.2%; HBV, 49.1%; vascular invasion or extrahepatic spread, 70.1%).
Median OS was 9.1 months on the linifanib arm (95% CI, 8.1 to 10.2) and 9.8
months on the sorafenib arm (95% CI, 8.3 to 11.0; hazard ratio [HR], 1.046; 95%
CI, 0.896 to 1.221). For prespecified stratification subgroups, OS HRs ranged
from 0.793 to 1.119 and the 95% CI contained 1.0. Median TTP was 5.4 months on
the linifanib arm (95% CI, 4.2 to 5.6) and 4.0 months on the sorafenib arm (95%
CI, 2.8 to 4.2; HR, 0.759; 95% CI, 0.643 to 0.895; P = .001). Best response rate
was 13.0% on the linifanib arm versus 6.9% on the sorafenib arm. Grade 3/4
adverse events (AEs); serious AEs; and AEs leading to discontinuation, dose
interruption, and reduction were more frequent with linifanib (all P < .001).
CONCLUSION: Linifanib and sorafenib had similar OS in advanced HCC. Predefined
superiority and noninferiority OS boundaries were not met for linifanib and the
study failed to meet the primary end point. TTP and ORR favored linifanib; safety
results favored sorafenib.
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