Study Identifies Factors Associated With Outcomes After Dabrafenib + Trametinib

Patients with melanoma treated with dabrafenib and trametinib who have normal lactate dehydrogenase (LDH) concentration and fewer than three organ sites containing metastases appear to have improved progression-free and overall survival, according to findings published in the journal The Lancet Oncology.1

Dabrafenib in combination with trametinib significantly improves outcomes compared with BRAF inhibitor monotherapy in patients with BRAF V600E-mutant or BRAF V600K-mutant advanced melanoma; however, many patients experience disease progression that often leads to death.

To determine subpopulations that may derive potentially greater benefit from treatment with this combination, researchers sought to identify clinical factors associated with long-term response and survival in patients with metastatic BRAF-mutant melanoma treated with dabrafenib and trametinib.

For the study, investigators retrospectively analyzed data from 617 patients who received the approved dose of trametinib and dabrafenib and were included in 3 randomized clinical trials.

Results showed that overall median progression-free survival (11.1 months [95% CI, 9.7-12.9]), median overall survival (25.6 months [95% CI, 23.1-34.3]), 1-year progression-free survival (48% [95% CI, 44-52]), 1-year overall survival (74% [95% CI, 71-78]), 2-year progression-free survival (30% [95% CI, 26-34]), and 2-year overall survival (53% [95% CI, 49-57]) were consistent with those in the individual trials.

Researchers found that patients with normal LDH and fewer than 3 organ sites containing metastases had the longest 1-year progression-free survival (68% [95% CI, 62-74]), 1-year overall survival (90% [95% CI, 87-94]), 2-year progression-free survival (46% [95% CI, 40-54]), and 2-year overall survival (75% [95% CI, 70-81]).

In contrast, patients with LDH concentration at least 2 times the upper limit of normal had the shortest 1-year progression survival (8% [95% CI, 3-19]), 1-year overall survival (40% [95% CI, 29-55]), 2-year progression-free survival (2% [95% CI, 0-13]), and 2-year overall survival (7% [95% CI, 3-19]).

The study also showed that among the 379 patients who experienced disease progression, those with progression in baseline or new non-CNS lesions had the longest survival after progression, while those with new CNS lesions or concurrent progression in baseline and new lesions had the shortest survival.

Reference

1. Long GV, Grob JJ, Nathan P, et al. Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials. Lancet Oncol. 2016 Nov 15. doi: 10.1016/S1470-2045(16)30578-2. [Epub ahead of print]

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