PD-1 or PD-L1 Blockade Adds Little to Combination of BRAF and MEK Inhibition in the Treatment of BRAF V600–Mutated Melanoma
Mené sur 267 patients atteints d'un mélanome présentant la mutation V600 du gène BRAF et de stade métastatique ou non résécable, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du spartalizumab (un anti-PD-1) à un traitement combinant dabrafénib et tramétinib
Most melanomas are driven by activation of the extracellular regulated kinase (ERK) pathway. In approximately 40% of cutaneous melanomas, this activation is due to a BRAF V600E or K mutation and these tumors are generally quite sensitive to treatment with the combination of a RAF inhibitor (RAFi) and a MEK inhibitor (MEKi). There are now three US Food and Drug Administration (FDA)–approved RAFi plus MEKi combinations, which have revolutionized the treatment of BRAF V600–mutated melanomas. They induce responses in 60%-80% of patients and are associated with improved overall survival (OS). Unfortunately, up to 80% of melanomas will develop resistance and progress at a median time of 12-15 months.
Journal of Clinical Oncology , éditorial en libre accès, 2021