title: Improvement of overall survival in stage IV melanoma patients during 2011-2014: analysis of real-world data in 441 patients of the German Central Malignant Melanoma Registry (CMMR).
abstract: BACKGROUND
  During 2011 and 2014, new treatment modalities like tyrosine kinase inhibitors and checkpoint inhibitors were introduced into the therapy of metastatic melanoma. This study addresses the question whether overall survival (OS) of metastatic melanoma patients has already been improved in 441 patients diagnosed with metastatic melanoma between 2011 and 2014 in the real-world setting at the University Hospital Tuebingen.
  
  
  METHODS
  All patients were documented with their different therapies by the CMMR and followed up until March 2016. Survival probabilities were calculated by Kaplan-Meier estimators, and log-rank tests were used to evaluate significances. Hazard ratios were estimated by Cox regression analysis for survival probabilities and prognostic factors in stage IV melanoma.
  
  
  RESULTS
  Best OS was observed in patients (n = 93) treated by metastasectomy as primary treatment with the intention to completely excise all metastases (3-year OS 61%). OS for patients with first-line systemic treatment (n = 258) was unfavorable in general (3-year OS 23%). Of those, the most favorable outcome was observed in patients without brain metastasis and treated with immunotherapy (mostly ipilimumab), as first-line treatment (median OS 35 months, 3-year OS 43%). In case of brain metastases, patients with targeted therapy had a better OS (median 14 months) than patients with ipilimumab treatment (median 7 months). Among all patients with first-line systemic treatment, outcome of patients diagnosed in the years 2013/2014, compared to 2011 and 2012, showed an improved survival. Three-year OS for patients that entered stage IV in 2013/2014 was 37% compared to those that entered stage IV in 2011 (18%) and 2012 (20%).
  
  
  CONCLUSIONS
  The analysis of real-world data of treatment of metastatic melanoma showed an improvement of OS with both immunotherapy and targeted therapy. In case of cerebral metastasis, patients treated with targeted therapy showed a longer median OS than patients treated with ipilimumab.
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Liebermeisterstr. 25, 72076, Tübingen, Germany. andrea.forschner@med.uni-tuebingen.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Forschner
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Liebermeisterstr. 25, 72076, Tübingen, Germany.|Graduate School of Life Sciences, Utrecht University, Utrecht, Netherlands.
authors.forename: Felizitas
authors.initials: F
authors.lastname: Eichner
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Liebermeisterstr. 25, 72076, Tübingen, Germany.|Portuguese Air Force Health Direction, Paço do Lumiar, 1649-020, Lisbon, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Amaral
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Liebermeisterstr. 25, 72076, Tübingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Keim
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Liebermeisterstr. 25, 72076, Tübingen, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Liebermeisterstr. 25, 72076, Tübingen, Germany.
authors.forename: Thomas Kurt
authors.initials: TK
authors.lastname: Eigentler
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000453:epidemiology* / Q000473:pathology / Q000556:secondary; D005260:Female; D005858:Germany; D006801:Humans; D000074324:Ipilimumab; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000453:epidemiology* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000074324:Ipilimumab
keywords: Brain metastasis; Checkpoint inhibitors; Chemotherapy; Ipilimumab; Melanoma; Nivolumab; Pembrolizumab; Survival; Targeted therapy