| General information |
| Database: | DB00965 |
| Objective: | Preclinical and early clinical studies have demonstrated that initial therapy with combined BRAF and MEK inhibition is more effective in BRAF(V600)mutant melanoma than singleagent BRAF inhibitors. This study assessed the safety and efficacy of dabrafenib and trametinib in patients who had received prior BRAF inhibitor treatment |
| Authors: | Johnson DB, et al |
| Title: | Combined BRAF (Dabrafenib) and MEK inhibition (Trametinib) in patients with BRAFV600mutant melanoma experiencing progression with singleagent BRAF inhibitor. |
| Journal: | J Clin Oncol. |
| Year: | 2014 |
| PMID: | 25287827 |
| Trial Design |
| Clinical Trial Id: | NCT01072175 |
| 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: | openlabelphase I/II study |
| Key Patients Feature: | patients with BRAFV600mutant melanoma experiencing progression with singleagent BRAF inhibitor |
| Biomarker: | BRAF V600mutant |
| Biomark Analysis: | Dabrafenib plus trametinib has modest clinical efficacy in patients with BRAF inhibitorresistant melanoma |
| Control Group Info: | single arm |
| Treatment Info: | patients treated with combination therapy after disease progression with BRAF inhibitor treatment administered before study enrollment (part B; n = 26) or after crossover at progression with dabrafenib monotherapy (part C; n = 45). |
| Primary End Point: | pharmacology, safety, and efficacy |
| Secondary End Point: | NA |
| Patients Number: | 71 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | In parts B and C, confirmed objective response rates (ORR) were 15% (95% CI, 4% to 35%) and 13% (95% CI, 5% to 27%), respectively |
| Disease Control Rate: | 65% in part B and 57% in part C |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | In part C, median progression free survival (PFS) was 3.6 months (95% CI, 2 to 4) |
| Median OS A vs. C: | In part C, median overall survival was 11.8 months (95% CI, 8 to 25) from crossover. |
| Adverse Event(agent arm): | The most frequent adverse events (AEs) were pyrexia, nausea/vomiting, and fatigue |
| Conclusions: | Dabrafenib plus trametinib has modest clinical efficacy in patients with BRAF inhibitorresistant melanoma. This regimen may be a therapeutic strategy for patients who previously benefited from BRAF inhibitor monotherapy more than and equal to 6 months but demonstrates minimal efficacy after rapid progression with BRAF inhibitor therapy. |