Entry Detail
| General information | |
| Database: | DB00185 |
| Objective: | Activating mutations in serinethreonine protein kinase BRAF (BRAF) are found in 50% of patients with advanced melanoma. Selective BRAFinhibitor therapy improves survival, as compared with chemotherapy, but responses are often shortlived. In previous trials, MEK inhibition appeared to be promising in this population. |
| Authors: | Flaherty KT, et al |
| Title: | Improved survival with MEK inhibition in BRAFmutated melanoma. |
| Journal: | N Engl J Med |
| Year: | 2012 |
| PMID: | 22663011 |
| Trial Design | |
| Clinical Trial Id: | NCT01245062 |
| Agent: | trametinib |
| Target: | MEK2 Dual specificity mitogenactivated protein kinase kinase 1 |
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase III openlabel trial |
| Key Patients Feature: | patients who had metastatic melanoma with a V600E or V600K BRAF mutation to receive either trametinib |
| Biomarker: | a V600E or V600K BRAF mutation |
| Biomark Analysis: | Trametinib, as compared with chemotherapy, improved rates of progression free and overall survival among patients who had metastatic melanoma with a BRAF V600E or V600K mutation |
| Control Group Info: | placebo |
| Treatment Info: | Patients received trametinib (2 mg orally) once daily or intravenous dacarbazine (1000 mg per square meter of bodysurface area) or paclitaxel (175 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to receive trametinib. |
| Primary End Point: | progression free survival |
| Secondary End Point: | overall survival |
| Patients Number: | 322 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4.8 vs 1.5(HR for disease progression or death in the trametinib group, 0.45; 95%[CI], 0.33 to 0.63; P<0.001). |
| Median OS A vs. C: | At 6 months, the rate of overall survival was 81% in the trametinib group and 67% in the chemotherapy group despite crossover (HR for death, 0.54; 95% CI, 0.32 to 0.92; P=0.01). |
| Adverse Event(agent arm): | Rash, diarrhea, and peripheral edema were the most common toxic effects in the trametinib group and were managed with dose interruption and dose reduction; asymptomatic and reversible reduction in the cardiac ejection fraction and ocular toxic effects occurred infrequently. Secondary skin neoplasms were not observed. |
| Conclusions: | Trametinib, as compared with chemotherapy, improved rates of progression free and overall survival among patients who had metastatic melanoma with a BRAF V600E or V600K mutation. |