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Factors Predictive of Outcomes With Dabrafenib/Trametinib in Metastatic BRAF-Mutant Melanoma

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Key Points

  • In patients with BRAF V600E–mutant or BRAF V600K–mutant metastatic melanoma, progression-free and overall survival were longest in patients with a baseline normal LDH and < 3 organ sites of metastasis.
  • Post-progression survival was longest in patients with disease progression in baseline or new non-CNS lesions.

Long et al identified factors predictive of progression-free and overall survival with combined dabrafenib (Tafinlar) plus trametinib (Mekinist) in patients with BRAF V600E–mutant or BRAF V600K–mutant metastatic melanoma, according to a pooled individual data analysis reported in The Lancet Oncology.

Study Details

The analysis included pooled data from 617 treatment-naive patients receiving the approved dose of dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) in the randomized BRF113220, COMBI-d, and COMBI-v trials. Patients with untreated brain metastases were not included in these trials.

Median follow-up was 20.0 months; 396 patients had disease progression or died, and 290 patients died. Median progression-free survival (11.1 months), median overall survival (25.6 months), 1-year progression-free survival (48%), 1-year overall survival (74%), 2-year progression-free survival (30%), and 2-year overall survival (53%) were consistent with overall findings in the individual trials.

Predictive Factors

One-year progression-free survival (68%) and overall survival (90%) and 2-year progression-free survival (46%) and overall survival (75%) were greatest in patients with a normal lactate dehydrogenase (LDH) level and < 3 organ sites with metastases (n = 237). Patients with an LDH level ≥ 2 times the upper limit of normal (n = 70) had the shortest 1-year progression-free survival (8%) and overall survival (40%) and 2-year progression-free survival (2%) and overall survival (7%). Among 379 patients with disease progression, post-progression survival was longest in 205 patients with disease progression in baseline lesions or new non–central nervous system (CNS) lesions (median = 10.0 months) and shortest in 171 patients with new CNS lesions or concurrent disease progression in baseline and new lesions (median = 4.0 months).

The investigators concluded: “Several patient and clinical characteristics at and after baseline are associated with outcomes with dabrafenib plus trametinib, and durable benefit is possible with targeted treatment in defined patient subsets.”

The study was funded by Novartis.

Georgina V. Long, BSc PhD MBBS FRACP, of the Melanoma Institute Australia, the University of Sydney, is the corresponding author of The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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