Entry Detail
| General information | |
| Database: | DB00099 |
| Objective: | No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib may be effective in hepatocellular carcinoma. |
| Authors: | Llovet JM, et al |
| Title: | Sorafenib in advanced hepatocellular carcinoma. |
| Journal: | N Engl J Med. |
| Year: | 2008 |
| PMID: | 18650514 |
| Trial Design | |
| Clinical Trial Id: | NCT00105443 |
| 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: | advanced hepatocellular carcinoma who had not received previous systemic treatment |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a largephase III, randomized, doubleblind, placebocontrolled trial conducted at IIII centers in III countries in Europe, North America, South America, and Australasia. |
| Key Patients Feature: | patients with advancedstage hepatocellular carcinoma, as confirmed by pathological analysis. None of the patients had received previous systemic therapy. Patients were classified as having advanced disease if were not eligible for or had disease progression after surgical or locoregional therapies. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | placebo:either 400 mg of sorafenib (consisting of two 200mg tablets) twice daily or matching placebo (both supplied by Bayer HealthCare Pharmaceuticals). |
| Treatment Info: | they randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. |
| Primary End Point: | overall survival and the time to symptomatic progression. |
| Secondary End Point: | the time to radiologic progression and safety |
| Patients Number: | 602 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | no significant difference in the median time to symptomatic progression (4.1 vs. 4.9, P=0.77). The median time to radiologic progression was 5.5 vs 2.8(P<0.001). |
| Median OS A vs. C: | 10.7 vs 7.9, HR 0.69; 95%CI, 0.55 to 0.87; P<0.001 |
| Adverse Event(agent arm): | Diarrhea, weight loss, handfoot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. |
| Conclusions: | In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo. |