| General information |
| Database: | DB00186 |
| Objective: | Combined BRAF and MEK inhibition, as compared with BRAF inhibition alone, delays the emergence of resistance and reduces toxic effects in patients who have melanoma with BRAF V600E or V600K mutations. |
| Authors: | Long GV, et al |
| Title: | Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. |
| Journal: | N Engl J Med. |
| Year: | 2014 |
| PMID: | 25265492 |
| Trial Design |
| Clinical Trial Id: | NCT01584648 |
| Agent: | dabrafenib
|
| Target: | BRaf protooncogene serine/threonineprotein kinase
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced BRAF(V600E/K) mut(+) melanoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | dabrafenib + trametinib |
| Study Type: | a phase III trial |
| Key Patients Feature: | previously untreated patients who had unresectable stage IIIC or stage IV melanoma with a BRAF V600E or V600K mutation |
| Biomarker: | a BRAF V600E or V600K mutation |
| Biomark Analysis: | NA |
| Control Group Info: | dabrafenib and placebo |
| Treatment Info: | pts received 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, response rate, response duration, and safety. A preplanned interim overall survival analysis was conducted. |
| Patients Number: | 423 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The overall response rate was 67% in the dabrafenibtrametinib group and 51% in the dabrafenibonly group (P=0.002). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median progression free survival was 9.3 months in the dabrafenibtrametinib group and 8.8 months in the dabrafenibonly group (hazard ratio for progression or death in the dabrafenibtrametinib group, 0.75; 95% confidence interval [CI], 0.57 to 0.99; P=0.03). |
| Median OS A vs. C: | At 6 months, the interim overall survival rate was 93% with dabrafenibtrametinib and 85% with dabrafenib alone (hazard ratio for death, 0.63; 95% CI, 0.42 to 0.94; P=0.02). |
| Adverse Event(agent arm): | Rates of adverse events were similar in the two groups, although more dose modifications occurred in the dabrafenibtrametinib group. The rate of cutaneous squamouscell carcinoma was lotheyr in the dabrafenibtrametinib group than in the dabrafenibonly group (2% vs. 9%), whereas pyrexia occurred in more patients (51% vs. 28%) and was more often severe (grade 3, 6% vs. 2%) in the dabrafenibtrametinib group. |
| Conclusions: | A combination of dabrafenib and trametinib, as compared with dabrafenib alone, improved the rate of progression free survival in previously untreated patients who had metastatic melanoma with BRAF V600E or V600K mutations. |