| General information |
| Database: | DB00180 |
| Objective: | Dabrafenib, an inhibitor of mutated BRAF, has clinical activity with a manageable safety profile in studies ofphase 1 and 2 in patients with BRAF(V600)mutated metastatic melanoma. They studied the efficacy of dabrafenib in patients with BRAF(V600E)mutated metastatic melanoma. |
| Authors: | Hauschild A, et al |
| Title: | Dabrafenib in BRAFmutated metastatic melanoma: a multicentre, openlabel, phase 3 randomised controlled trial. |
| Journal: | Lancet. |
| Year: | 2012 |
| PMID: | 22735384 |
| Trial Design |
| Clinical Trial Id: | NCT01227889 |
| Agent: | dabrafenib
|
| Target: | BRaf protooncogene serine/threonineprotein kinase
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced BRAF(V600E/K) mut(+) melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a openlabelphase III trial |
| Key Patients Feature: | Patients aged 18 years or older with previously untreated, stage IV or unresectable stage III BRAF(V600E) mutationpositive melanoma |
| Biomarker: | BRAF(V600E) mutationpositive |
| Biomark Analysis: | NA |
| Control Group Info: | dacarbazine |
| Treatment Info: | Pts were randomly assigned (3:1) to receive dabrafenib (150 mg twice daily, orally) or dacarbazine (1000 mg/m(2) intravenously every 3 weeks). |
| Primary End Point: | investigatorassessed progression free survival; safety was assessed per protocol. |
| Secondary End Point: | NA |
| Patients Number: | 733 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 93%(50%, 42.4-57.1)vs 4%(6%, 1.8-15.5) |
| Disease Control Rate: | Complete response:6(3%) vs 1(2%);Partial response: 87 (47%)vs 3 (5%);Stable disease:78 (42%)vs 30 (48%) |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median progression free survival was 5..1 months for dabrafenib and 2.7 months for dacarbazine, with a hazard ratio (HR) of 0.30 (95% CI 0.180.51; p<0.0001). |
| Median OS A vs. C: | 30 patients died (21 [11%] patients in the dabrafenib group and 9 [14%] patients in the dacarbazine group). The overall survival HR was 0.61 (95% CI 0.25-1.48) in favour of dabrafenib; additional followup is ongoing. |
| Adverse Event(agent arm): | Treatmentrelated adverse events (grade 2 or higher) occurred in 100 (53%) of the 187 patients who received dabrafenib and in 26 (44%) of the 59 patients who received dacarbazine. The most common adverse events with dabrafenib were skinrelated toxic effects, fever, fatigue, arthralgia, and headache. Grade 34 adverse events were uncommon |
| Conclusions: | Dabrafenib significantly improved progression free survival compared with dacarbazine. |