| General information |
| Database: | DB00961 |
| Objective: | Previously, a study of ours showed that the combination of dabrafenib and trametinib improves progression free survival compared with dabrafenib and placebo in patients with BRAF Val600Lys/Glu mutationpositive metastatic melanoma. The study was continued to assess the secondary endpoint of overall survival, which they report in this Article. |
| Authors: | Long GV, et al |
| Title: | Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAFmutant melanoma: a multicentre, doubleblind, phase 3 randomised controlled trial. |
| Journal: | Lancet. |
| Year: | 2015 |
| PMID: | 26037941 |
| Trial Design |
| Clinical Trial Id: | NCT01584648 |
| Agent: | Dabrafenib trametinib
|
| Target: | NA
|
| Cancer Type: | melanoma |
| Cancer Subtype: | BRAF V600mutant melanoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | Dabrafenib+trametinib |
| Study Type: | a multicentre, doubleblind, phase III randomised controlled trial. |
| Key Patients Feature: | previously untreated patients with BRAF Val600Glu or Val600Lys mutationpositive unresectable stage IIIC or stage IV melanoma. |
| Biomarker: | Val600 BRAFmutant |
| Biomark Analysis: | The improvement in overall survival establishes the combination of dabrafenib and trametinib as the standard targeted treatment for BRAF Val600 mutationpositive melanoma. |
| Control Group Info: | Dabrafenib and trametinib versus dabrafenib and placebo |
| Treatment Info: | Participants were computerrandomised (1:1) to receive a combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily), or dabrafenib and placebo. |
| Primary End Point: | progression free survival |
| Secondary End Point: | overall survival |
| Patients Number: | 947 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 11.0 months (95% CI 8.013.9) in the dabrafenib and trametinib group and 8.8 months (5.99.3) in the dabrafenib only group (HR 0.67, 95% CI 0.530.84; p=0.0004; unadjusted for multiple testing). |
| Median OS A vs. C: | 25.1 months (95% CI 19.2not reached) in the dabrafenib and trametinib group versus 18.7 months (15.223.7) in the dabrafenib only group (hazard ratio [HR] 0.71, 95% CI 0.550.92; p=0.0107). |
| Adverse Event(agent arm): | The most common treatmentrelated adverse events were pyrexia, chills, fatigue, rash, and nausea in the dabrafenib and trametinib group, and hyperkeratosis, fatigue, handfoot syndrome, alopecia, pyrexia, and arthralgia in the dabrafenib only group . |
| Conclusions: | The improvement in overall survival establishes the combination of dabrafenib and trametinib as the standard targeted treatment for BRAF Val600 mutationpositive melanoma. Studies assessing dabrafenib and trametinib in combination with immunotherapies are ongoing |