In advanced melanoma with a BRAF mutation, the combination of two tablets, dabrafenib and trametinib, kept about a third of patients alive after 5 years. Patients whose tumour disappeared completely (about 1 in 5) had the best results. Today, combination immunotherapy is usually preferred as the first treatment, and these tablets are used when a quick response is needed or immunotherapy is not suitable.
Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation; first line if anti-PD-1–based therapy is not suitable, or after failure of immunotherapy
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Dabrafenib | 150 mg twice daily | Oral, on an empty stomach | Daily, continuously |
| Trametinib | 2 mg once daily | Oral, on an empty stomach | Daily, continuously |
Per the FDA labels; evidence:.
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Dabrafenib 150 mg orally twice daily + trametinib 2 mg orally once daily, continuously until progression or unacceptable toxicity (211 patients in COMBI-d and 352 patients in COMBI-v). Comparator groups in the parent trials: dabrafenib 150 mg twice daily + placebo (COMBI-d) and vemurafenib 960 mg orally twice daily (COMBI-v).
Source of the regimen details: Abstract of the paper, ClinicalTrials.gov NCT01584648 and NCT01597908, and the FDA label (TAFINLAR)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Adults with unresectable stage IIIC or stage IV cutaneous melanoma with a BRAF V600E or V600K mutation (central testing), with measurable disease (RECIST 1.1) and ECOG 0 or 1, without previous systemic therapy for advanced disease (previous adjuvant therapy allowed) and without previous BRAF or MEK inhibitors; ocular or mucosal melanoma and untreated brain metastases were excluded (ClinicalTrials.gov).
Primary endpoints of the parent trials: progression-free survival (COMBI-d) and overall survival (COMBI-v). In this analysis: 4- and 5-year progression-free and overall survival and factors associated with long-term benefit.
The safety profile of dabrafenib + trametinib is well known (pyrexia, fatigue, chills, nausea, rash and elevated liver enzymes). According to the FDA label, in the pooled metastatic disease population pyrexia occurred in 58% of patients and in 5% was accompanied by hypotension, rigors, dehydration or renal failure.
This analysis showed that BRAF–MEK inhibition can produce long-term control in a subset of patients. However, the DREAMseq and SECOMBIT trials showed that starting with combination immunotherapy gives better survival; the ESMO 2025 guideline considers nivolumab–ipilimumab the preferred first-line option for all patients regardless of BRAF status (if it can be tolerated) and proposes BRAF–MEK inhibition for patients who need a rapid response or cannot receive immunotherapy.
The analysis is pooled and descriptive; there is no direct comparison group with immunotherapy; some patients received immunotherapy after progression, which affects overall survival.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
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