In this study, patients with stage 3 melanoma with a BRAF V600 mutation whose tumour had been removed by surgery were given two oral drugs (dabrafenib and trametinib) or a placebo for one year. After nearly 10 years of follow-up, the chance of the disease coming back and spreading to distant parts of the body was lower with these two drugs. A reduction in the risk of death was seen, but across all patients it was not statistically certain; in patients with the BRAF V600E mutation this reduction was larger. No new side effects were seen compared with earlier reports.
Stage III melanoma with lymph node involvement and a BRAF V600 mutation after complete resection; ESMO 2025 recommends it only for V600E mutations (not V600K)
| 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 and place in therapy:.
On the page “Melanoma (skin cancer)” · Resectable melanoma: neoadjuvant and adjuvant
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 for 12 months (or until relapse or unacceptable toxicity). According to the FDA label, both drugs are taken on an empty stomach and are interrupted for a fever of 38 °C or higher.
Two matching oral placebos for 12 months.
Source of the regimen details: Abstract of the paper, ClinicalTrials.gov NCT01682083 and the FDA labels (TAFINLAR, MEKINIST)
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 high-risk stage III cutaneous melanoma (IIIA with lymph node metastasis larger than 1 mm, IIIB or IIIC per AJCC 7th edition) with a BRAF V600E or V600K mutation (confirmed by the central laboratory), rendered disease-free by complete surgery (including complete lymph node dissection) no more than 12 weeks before randomisation; ECOG 0 or 1; no previous anticancer therapy (including radiotherapy). Mucosal or ocular melanoma, unresectable in-transit metastases and distant metastases were excluded (ClinicalTrials.gov NCT01682083).
This final report gives the results for overall survival, melanoma-specific survival, relapse-free survival and distant metastasis-free survival.
No new safety signal was seen in this final report, and the findings were consistent with previous reports. According to the FDA label, the most common adverse events in COMBI-AD (20% or more) were pyrexia, fatigue, nausea, headache, rash, chills, diarrhoea, vomiting, arthralgia and myalgia; adverse events led to discontinuation of trametinib in 24%, interruption in 54% and dose reduction in 23% of patients (most common cause: pyrexia).
These final results confirm the durability of the benefit of adjuvant dabrafenib plus trametinib in relapse-free survival and distant metastasis-free survival. The overall survival benefit in the whole population was not significant, so decisions should be individualised, taking other adjuvant treatment options into account. Approval status and guideline recommendations should be checked separately, as the abstract does not address them.
The overall survival benefit in the whole population was not statistically significant (P=0.06). The BRAF V600E subgroup result is a subgroup analysis and should be interpreted with caution. Follow-up duration differed between the two groups (8.33 versus 6.87 years).
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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