Targeted Therapy for Cutaneous Melanoma

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Targeted BRAF and MEK dual inhibition (BRAFi /MEKi) in BRAF V600 mutant melanoma:
    • Has been associated with relatively rapid response, high disease control rates, and a survival benefit in stage IV melanoma
    • Unfortunately, this approach has also been associated with limited durability of response, leading some investigators to examine alternate stages of disease for this regimen
  • Long et al. investigated the efficacy of these agents in the adjuvant stage III setting:
    • In a randomized, double-blind, placebo-controlled, phase III trial (COMBI-AD):
      • That randomly assigned patients with completely resected stage III melanoma and BRAF V600 mutations (n = 870) to receive:
        • Oral dabrafenib (150 mg BID) plus trametinib (2 mg once daily) versus placebo in a 1:1 fashion
      • At a median follow-up of 2.8 years:
        • The estimated 3-year RFS was 58% in the combination-therapy group and 39% in the placebo group (HR for relapse or death, 0.47; 95% CI, 0.39 to 0.58; P < .001)
        • In addition, the BRAFi / MEKi group had a significantly higher 3-year OS of 86% versus 77% in the placebo group (HR for death, 0.57; 95% CI, 0.42 to 0.79; P = .0006)
      • Authors noted that this level of improvement did not cross the prespecified interim analysis boundary of P = .000019
      • They concluded that combined dabrafenib plus trametinib in the adjuvant setting resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF V600 mutations and with an acceptable toxicity profile
  • This trial led to the 2018 FDA approval of dabrafenib / trametinib:
    • For use in the adjuvant setting for those with stage III disease and BRAF V600E or V600K mutations
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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