Format

Send to

Choose Destination
J Clin Oncol. 2015 Jan 10;33(2):172-9. doi: 10.1200/JCO.2013.54.3298. Epub 2014 Dec 8.

Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial.

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.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01009593.

PMID:
25488963
PMCID:
PMC4279237
DOI:
10.1200/JCO.2013.54.3298
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center