| General information |
| Database: | DB00187 |
| Objective: | The BRAF inhibitors vemurafenib and dabrafenib have shown efficacy as monotherapies in patients with previously untreated metastatic melanoma with BRAF V600E or V600K mutations. Combining dabrafenib and the MEK inhibitor trametinib, as compared with dabrafenib alone, enhanced antitumor activity in this population of patients. |
| Authors: | Robert C, et al |
| Title: | Improved overall survival in melanoma with combined dabrafenib and trametinib. |
| Journal: | N Engl J Med. |
| Year: | 2015 |
| PMID: | 25399551 |
| Trial Design |
| Clinical Trial Id: | NCT01597908 |
| 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 or vemurafenib |
| Study Type: | an openlabel, phase III trial |
| Key Patients Feature: | patients with metastatic melanoma with a BRAF V600 mutation |
| Biomarker: | BRAF V600 mutation |
| Biomark Analysis: | NA |
| Control Group Info: | dabrafenib+placebo |
| Treatment Info: | receive either a combination of dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) or vemurafenib (960 mg twice daily) orally as firstline therapy. |
| Primary End Point: | overall survival. |
| Secondary End Point: | NA |
| Patients Number: | 704 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The objective response rate was 64% in the combinationtherapy group and 51% in the vemurafenib group (P<0.001). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was 11.4 months in the combinationtherapy group and 7.3 months in the vemurafenib group (HR 0.56; 95% CI, 0.46 to 0.69; P<0.001). |
| Median OS A vs. C: | OS rate at 12 months was 72% (95% [CI], 67 to 77) in the combinationtherapy group and 65% (95% CI, 59 to 70) in the vemurafenib group (HR for death in the combinationtherapy group, 0.69; 95% CI, 0.53 to 0.89; P=0.005). |
| Adverse Event(agent arm): | Rates of severe adverse events and studydrug discontinuations were similar in the two groups. Cutaneous squamouscell carcinoma and keratoacanthoma occurred in 1% of patients in the combinationtherapy group and 18% of those in the vemurafenib group. |
| Conclusions: | Dabrafenib plus trametinib, as compared with vemurafenib monotherapy, significantly improved overall survival in previously untreated patients with metastatic melanoma with BRAF V600E or V600K mutations, without increased overall toxicity. |