title: Survival of patients with metastatic melanoma and brain metastases in the era of MAP-kinase inhibitors and immunologic checkpoint blockade antibodies: A systematic review.
abstract: BACKGROUND
  The incidence of brain metastases (BM) in melanoma patients is common and associated with poor prognosis. MAP-kinase inhibitors and immunologic checkpoint blockade antibodies led to improved survival of metastatic melanoma patients; however, patients with BM are under-represented or excluded from the majority of clinical trials and the impact of new drugs on their survival is less clear. With the present systematic review, we aimed to analyze outcomes of patients with melanoma BM treated with the new drugs, both in the setting of phase I-II-III clinical trials and in the "real world".
  
  
  METHODS
  An electronic search was performed to identify studies reporting survival outcomes of patients with melanoma BM treated with MAP-kinase inhibitors and/or immunologic checkpoint blockade antibodies, regardless of study design.
  
  
  RESULTS
  Twenty-two studies were included for a total of 2153 patients. Median OS was 7.9 months in phase I-II-III trials and 7.7 months in "real world" studies. In clinical trials, median OS was 7.0 months for patients treated with immunotherapy and 7.9 months for patients treated with BRAF inhibitors. In "real world" studies, median OS was 4.3 months and 7.7 months for patients treated with immunotherapy and BRAF inhibitors, respectively. Evidence of clinical activity exists for both immunotherapy and MAP-kinase inhibitors.
  
  
  CONCLUSIONS
  MAP-kinase inhibitors and immunologic checkpoint blockade antibodies have clinical activity and may achieve improved OS in patients with metastatic melanoma and BM. These results support the inclusion of patients with BM in investigations of new agents and new treatment regimens for metastatic melanoma.
authors.affiliation: Department of Plastic and Reconstructive Surgery, IRCCS AOU San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. Electronic address: francesco.spagnolo85@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Spagnolo
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Picasso
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lambertini
authors.affiliation: Department of Plastic and Reconstructive Surgery, St George's Hospital, London, UK.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ottaviano
authors.affiliation: Clinical Epidemiology Unit, IRCCS AOU San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Dozin
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Queirolo
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000556:secondary; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D009367:Neoplasm Staging; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D048493:Proto-Oncogene Proteins B-raf
keywords: Brain metastases; Dabrafenib; Ipilimumab; Melanoma; Survival; Vemurafenib