Certain Factors Prognostic in Dabrafenib/Trametinib-Treated Melanoma

November 30, 2016

Researchers have identified characteristics associated with improved outcomes when treating BRAF-mutated advanced melanoma with the combination of dabrafenib and trametinib.

Researchers have identified several patient and clinical characteristics associated with improved outcomes when treating BRAF V600E– and BRAF V600K–mutated advanced melanoma with the combination of dabrafenib and trametinib. Looking at pooled data from three randomized trials of the drug combination, baseline lactate dehydrogenase (LDH) concentration, number of organ sites with metastases, or both were identified as the best baseline predictors of progression-free and overall survival from the disease. These results were published in Lancet Oncology.

“In the pooled dataset, 2-year overall survival was 53% and 2-year progression-free survival was 30%, which is consistent with that previously reported for individual trials,” wrote Georgina V. Long, MD, of the Melanoma Institute Australia at the University of Sydney, and colleagues. “In the most favorable subgroup identified, patients with normal LDH concentration and fewer than three organ sites with metastasis at baseline had an overall survival of 75% and progression-free survival of 46% at 2 years.”

According to Long and colleagues, treatment with the combination of dabrafenib and trametinib provides patients with BRAF-mutated melanoma significant benefit compared with BRAF inhibitor monotherapy. However, because the disease will ultimately progress, more research was needed to identify factors associated with long-term response and survival after treatment with these drugs.

The researchers conducted a retrospective study looking at data from three randomized trials that included 617 patients with treatment-naive BRAF V600E– or BRAF V600K–mutated metastatic melanoma. All patients received the approved dose of 150-mg dabrafenib twice daily plus 2-mg trametinib once daily. The median follow-up was 20 months.

During study follow-up periods, 396 patients experienced progression events and 290 patients died. The median progression-free survival was 11.1 months and the median overall survival was 25.6 months. Pooled 1-year and 2-year progression-free and overall survival rates were similar to those in the individual trials.

When looking for patient characteristics to predict response, the researchers found that those patients with normal LDH concentration and less than three organ sites with metastases had the longest 1-year progression-free survival (68%) and overall survival (90%) rates, and 2-year progression-free survival (46%) and overall survival (75%) rates. In contrast, those patients with LDH concentrations at 2 times the upper limit of normal had the shortest 1-year progression-free and overall survival rates (8% and 40%) and 2-year progression-free and overall survival rates (2% and 7%).

“Whether LDH concentration is simply a marker of aggressive disease or has a direct causative role in tumor growth or response to treatment is not known, but is the subject of translational research,” the researchers noted.

Among the patients whose disease progressed during follow-up, survival was longest in those with progression in baseline or new non–central nervous system lesions, with a median survival of 10 months. Survival was shortest in those with new central nervous system lesions or concurrent progression in baseline and new lesions, with a median survival of 4 months.

“Comparison of these results with future datasets for other melanoma treatments are needed to establish whether factors associated with prolonged survival and response identified in this study apply to patients receiving other treatments, or if they are prognostic,” the researchers concluded.