Entry Detail
| General information | |
| Database: | DB00918 |
| Objective: | In Japan and South Korea, transarterial chemoembolisation (TACE) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma (hepatocellular carcinoma). Sorafenib, a multikinase inhibitor, has been shown effective and safe in patients with advanced hepatocellular carcinoma. Thisphase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable hepatocellular carcinoma who responded to TACE. |
| Authors: | Kudo M, et al |
| Title: | Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma. |
| Journal: | Eur J Cancer. |
| Year: | 2011 |
| PMID: | 21664811 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | liver cancer |
| Cancer Subtype: | hepatocellular carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 16 |
| Therapeutic Combination Content: | transarterial chemoembolisation+sorafenib |
| Study Type: | Phase III study |
| Key Patients Feature: | Patients (n=458) with unresectable hepatocellular carcinoma, ChildPugh class A cirrhosis and more than and equal to 25% tumour necrosis/shrinkage 13 months after 1 or 2 TACE sessions |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | sorafenib versus placebo |
| Treatment Info: | patients were randomised 1:1 to sorafenib 400mg bid or placebo and treated until progression/recurrence or unacceptable toxicity. |
| Primary End Point: | time to progression/recurrence (TTP). |
| Secondary End Point: | overall survival (OS). |
| Patients Number: | 458 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | in the sorafenib and placebo groups was 5.4 and 3.7 months, respectively (hazard ratio (HR), 0.87; 95% confidence interval (CI), 0.701.09; P=0.252). |
| Median PFS A vs. C: | The 3month progression free rates in the sorafenib and placebo groups were 65.0% and 58.7%, respectively, and their 6month progression free rates were 45.7% and 33.5%, respectively. |
| Median OS A vs. C: | 29.7 months in the sorafenib group (95% CI, 28.6 months - not yet reached) but had not yet been reached in the placebo group (HR [sorafenib/placebo], 1.06; 95% CI, 0.69-1.64; P = 0.790). |
| Adverse Event(agent arm): | Most DRAEs were mild to moderate (Table 3), with the most frequent in the sorafenib and placebo groups being HFSR (82% versus 7%), elevated lipase (44% versus 8%), alopecia (41% versus 3%) and rash/desquamation (40% versus 11%). In the sorafenib group, 24% and 4% of patients experienced grades 3 and 4 elevated lipase, respectively, compared with 3% and <1%, respectively, in the placebo group. There was no radiographic or clinical evidence of pancreatitis in either group. The overall incidences of grade 3 HFSR (protocoldefined scale) in the sorafenib and placebo groups were 35% and 0%, respectively, and the overall incidence of serious DRAEs was 18% and 9%, respectively. There were no drugrelated deaths. |
| Conclusions: | This trial, conducted prior to the reporting of registrationalphase III trials, found that sorafenib did not significantly prolong TTP in patients who responded to TACE. This may have been due to delays in starting sorafenib after TACE andor low daily sorafenib doses |