Melanoma Patients Treated With Dabrafenib, Trametinib Have Overall Survival Rates of More Than 2 Years

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A combination of 2 MAPK-inhibitors, dabrafenib and trametinib, significantly improved overall survival rates in BRAF V600E-mutant metastatic melanoma.
A combination of 2 MAPK-inhibitors, dabrafenib and trametinib, significantly improved overall survival rates in BRAF V600E-mutant metastatic melanoma.

Patients with BRAF V600E-mutant metastatic melanoma who were treated with a combination of the mitogen-activated protein kinase (MAPK) inhibitors dabrafenib and trametinib demonstrated significant improvement in overall and progression-free survival.1

In this study, investigators sought to report the overall survival (OS) and clinical characteristics of BRAF inhibitor-naïve patients with BRAF V600 mutation-positive metastatic melanoma treated with dabrafenib plus trametinib. There were 2 cohorts: non-randomly assigned patients (part B; 24 patients) and randomly assigned patients (part C; 54 patients). Both cohorts received dabrafenib 150 mg twice daily plus trametinib 2 mg daily.


“This study is the longest-term data we have for combined targeted therapy,” said lead study author Georgina Long, MD, PhD, of the University of Sydney and Melanoma Institute Australia, Sydney, in an interview with Cancer Therapy Advisor.

Results showed that median OS was 27.4 months for those in part B and 25.0 months for patients in part C. At 1, 2, and 3 years, OS was 72%, 60%, and 47%, respectively, and 80%, 51%, and 38%, respectively.

“[This is] a cancer that until 4 years ago, had a 1 year survival of only 20% to 30%,” said Dr Long.

Dr Long and colleagues found that when treated with the combination of dabrafenib and trametinib, median progression-free survival (PFS) for patients in part B was 10.8 months vs 9.4 months for those in part C. At years 1, 2, and 3, patients in part B had a PFS rate of 44%, 22%, and 18%, respectively; and 41%, 25%, and 21% for those in part C.

“The combination has an acceptable long-term safety profile and is a standard of care for patients with BRAF mutation–positive metastatic melanoma, particularly given the recent publications demonstrating a significant improvement in the PFS and OS in phase III trials of combination versus single-agent BRAF inhibitors,” the authors wrote.

RELATED: No Survival Benefit for Adjuvant HDI in Single Positive SLN Melanoma

The study also examined patients' baseline prognostic features to determine whether there was any correlation between them and overall survival. Baseline characteristics examined included lactate dehydrogenase (LDH) levels, number of metastatic sites, Eastern Cooperative Oncology Group performance status, prior immunotherapy, and earlier-stage melanoma.

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