| General information |
| Database: | DB00103 |
| Objective: | This openlabelphase 3 trial evaluated efficacy and tolerability of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (hepatocellular carcinoma) without prior systemic therapy. |
| Authors: | Cainap C, et al |
| Title: | Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomizedphase III trial. |
| Journal: | J Clin Oncol. |
| Year: | 2015 |
| PMID: | 25488963 |
| Trial Design |
| Clinical Trial Id: | NCT01009593. |
| Agent: | linifanib
|
| Target: | Macrophage colonystimulating factor 1
|
| Cancer Type: | liver cancer |
| Cancer Subtype: | advanced hepatocellular carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an Openlabel, phase III trial |
| Key Patients Feature: | advanced or metastatic hepatocellular carcinoma who had not received prior systemic therapy at 186 sites by 207 investigators in 28 countries worldwide(median age, 60 years; Asian, 66.6%; ECOG PS 0, 65.2%; HBV, 49.1%; vascular invasion or extrahepatic spread, 70.1%) |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | sorafenib 400 mg twice daily |
| Treatment Info: | Patients were randomly assigned in a 1:1 ratio to linifanib 17.5 mg once daily or sorafenib 400 mg twice daily. |
| Primary End Point: | OS |
| Secondary End Point: | TTP and objective response rate (ORR). |
| Patients Number: | 1035 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Best response rate was 13.0% on the linifanib arm vs 6.9% on the sorafenib arm. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median TTP:5.4 vs 4.0 HR, 0.759; 95% CI, 0.643 to 0.895; P = .001 |
| Median OS A vs. C: | 9.1 vs 9.8 [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. |
| Adverse Event(agent 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). |
| Conclusions: | Linifanib and sorafenib had similar OS in advanced hepatocellular carcinoma. 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. |