First line treatment of BRAF mutated advanced melanoma: Does one size fit all?

Federica Giugliano, Edoardo Crimini, Paolo Tarantino, Paola Zagami, Jacopo Uliano, Chiara Corti, Dario Trapani, Giuseppe Curigliano, Paolo A Ascierto

Research output: Contribution to journalReview articlepeer-review


In the last decade, immunotherapy and target therapy have revolutionized the prognosis of patients with BRAF-V600 mutation-positive metastatic melanoma. To date, three different combinations of BRAF/MEK inhibitors have been approved for this population, showing comparable efficacy and unique toxicity profiles. Several immune-checkpoint inhibitors, including pembrolizumab, nivolumab and the combination of nivolumab plus ipilimumab, are also available options for untreated metastatic melanoma patients. A novel approach has emerged by combining immune-checkpoint inhibitors and targeted agents, based on preclinical hints of synergy, prompting clinical results from large randomized trials. Specifically, the triplet of atezolizumab, vemurafenib and cobimetinib has been recently approved by FDA for patients with untreated BRAF-mutant metastatic melanoma. With a wide variety of available treatment options in this setting, it is paramount to establish criteria to select the most effective and safe frontline tailored approaches, for each patient. Results from ongoing studies are awaited, to maximise the benefits in survival outcomes and quality of life for patients, balancing adverse events and clinical benefit. The purpose of this review is to summarize the current landscape of standard and experimental treatment strategies for the first line treatment of patients with BRAF-mutated advanced melanoma and discuss the best patient-centered tailored strategies in the first-line setting.

Original languageEnglish
Pages (from-to)102253
JournalCancer Treat. Rev.
Publication statusPublished - Sept 2021


  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Clinical Trials, Phase III as Topic
  • Humans
  • Immune Checkpoint Inhibitors/administration & dosage
  • MAP Kinase Signaling System/drug effects
  • Melanoma/drug therapy
  • Molecular Targeted Therapy
  • Mutation
  • Protein Kinase Inhibitors/administration & dosage
  • Proto-Oncogene Proteins B-raf/antagonists & inhibitors
  • Randomized Controlled Trials as Topic
  • Skin Neoplasms/drug therapy
  • Treatment Outcome


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