Adjuvant Dabrafenib plus Trametinib in Stage IIIBRAF-Mutated Melanoma

Abstract

Adjuvant use of combination therapy with dabrafenib plus trametinib resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF V600E or V600K mutations than the adjuvant use of placebo and was not associated with new toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov, NCT01682083 ; EudraCT number, 2012-001266-15 .).

Melanoma Staging: American Joint Committee on Cancer (AJCC) 8th Edition and Beyond

“…25,26 Microscopic tumor burden has already been implemented as an inclusion criterion in some clinical trials of adjuvant therapy. 5 Based on available data and practical considerations, the AJCC melanoma expert panel recommends that the single largest maximum dimension (measured in millimeters using an ocular micrometer) of the largest discrete metastatic melanoma deposit in any tumor-involved SLN be recorded in pathology reports. Although this histopathological parameter is not currently a formal staging criterion, SLN tumor burden will be included in and will likely guide the development of future prognostic models and ultimately validated clinical tools (e.g., calculators, nomograms, etc.)…”

Vulvar melanoma: management of primary disease and repeated recurrences

“…7 Adjuvant combined BRAF and MEK inhibition in patients with BRAF V600E, or V600K mutations resulted in a significant improvement in relapse-free survival as compared with placebo (HR 0.47, 95% CI 0.39 to 0.58 ). 8 The combined use of dabrafenib and trametinib led to a 3- year recurrence-free survival of 58 % compared with 39 % in those receiving the placebo. …”

Cardiotoxicity mechanisms of the combination of BRAF-inhibitors and MEK-inhibitors

“…No data were reported along the full-text about decreased ejection fraction, dyspnoea, QT-interval prolongation and asymptomatic increased creatine kinase (see Table 1). (Long et al, 2017) Very different data about cardiovascular toxicity emerged from a phase 2 trial in which this combination therapy was studied in the neoadjuvant setting: fatigue grade 1-2 in 85%, hypertension grade 1-2 in 54%, grade 3 atrial fibrillation in 8%, grade 3 syncope in 8%. This was probably due to the small number of patients, because only 13 patients received the treatment Dabrafenib and Trametinib.…”