title: Survival of patients with advanced metastatic melanoma: The impact of novel therapies.
abstract: The survival of advanced metastatic melanoma has been greatly improved within the past few years. New therapeutic strategies like kinase inhibitors for BRAF-mutant melanoma and immune checkpoint blockers proved to prolong survival times within clinical trials, and many of them have already entered routine clinical use. However, these different treatment modalities have not yet been tested against each other, which complicate therapy decisions. We performed an explorative analysis of survival data from recent clinical trials. Thirty-five Kaplan-Meier survival curves from 17 trials were digitised, re-grouped by matching inclusion criteria and treatment line, and averaged by therapy strategy. Notably, the survival curves grouped by therapy strategy revealed a very high concordance, even if different agents were used. The greatest survival improvement was observed with the combination of BRAF plus MEK inhibitors as well as with Programmed-death-1 (PD1) blockers with or without cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockers, respectively, with these two treatment strategies showing similar survival outcomes. For first-line therapy, averaged survival proportions of patients alive at 12 months were 74.5% with BRAF plus MEK inhibitor treatment versus 71.9% with PD-1 blockade. This explorative comparison shows the kinase inhibitors as similarly effective as immune checkpoint blockers with regard to survival. However, to confirm these first trends for implementation into an individualised treatment of melanoma patients, data from prospective clinical trials comparing the different treatment strategies head-to-head have to be awaited.
authors.affiliation: Department of Dermatology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. Electronic address: selma.ugurel@uk-essen.de.
authors.forename: Selma
authors.initials: S
authors.lastname: Ugurel
authors.affiliation: 28355 Bremen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Röhmel
authors.affiliation: Melanoma, Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori, Fondazione "G. Pascale", Naples, Italy.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.affiliation: Dermatology Department, Timone Hospital and Aix-Marseille University, Marseille, France.
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Grob
authors.affiliation: University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Hauschild
authors.affiliation: Royal Marsden Hospital NHS Foundation Trust, London, UK.
authors.forename: James
authors.initials: J
authors.lastname: Larkin
authors.affiliation: Melanoma Institute Australia and The University of Sydney, Sydney, NSW, Australia.
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Long
authors.affiliation: University of Manchester, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Lorigan
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; University of Melbourne, Parkville, VIC, Australia.
authors.forename: Grant A
authors.initials: GA
authors.lastname: McArthur
authors.affiliation: University of California, Los Angeles, CA, USA.
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif Grand-Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.affiliation: Department of Dermatology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Center for Dermatooncology, Department of Dermatology, University Tuebingen, 72074 Tuebingen, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000188:drug therapy / Q000401:mortality* / Q000556:secondary; D058990:Molecular Targeted Therapy / Q000401:mortality; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D035703:Therapies, Investigational / Q000401:mortality
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D047428:Protein Kinase Inhibitors
keywords: Immune checkpoint blockers; Kinase inhibitors; Melanoma; Survival; Therapy