title: SWITCH: A Randomised, Sequential, Open-label Study to Evaluate the Efficacy and Safety of Sorafenib-sunitinib Versus Sunitinib-sorafenib in the Treatment of Metastatic Renal Cell Cancer.
abstract: BACKGROUND
  Understanding how to sequence targeted therapies for metastatic renal cell carcinoma (mRCC) is important for maximisation of clinical benefit.
  
  
  OBJECTIVE
  To prospectively evaluate sequential use of the multikinase inhibitors sorafenib followed by sunitinib (So-Su) versus sunitinib followed by sorafenib (Su-So) in patients with mRCC.
  
  
  METHODS
  The multicentre, randomised, open-label, phase 3 SWITCH study assessed So-Su versus Su-So in patients with mRCC without prior systemic therapy, and stratified by Memorial Sloan Kettering Cancer Center risk score (favourable or intermediate).
  
  
  METHODS
  Patients were randomised to sorafenib 400mg twice daily followed, on progression or intolerable toxicity, by sunitinib 50mg once daily (4 wk on, 2 wk off) (So-Su), or vice versa (Su-So).
  
  
  METHODS
  The primary endpoint was improvement in progression-free survival (PFS) with So-Su versus Su-So, assessed from randomisation to progression or death during second-line therapy. Secondary endpoints included overall survival (OS) and safety.
  
  
  CONCLUSIONS
  In total, 365 patients were randomised (So-Su, n=182; Su-So, n=183). There was no significant difference in total PFS between So-Su and Su-So (median 12.5 vs 14.9 mo; hazard ratio [HR] 1.01; 90% confidence interval [CI] 0.81-1.27; p=0.5 for superiority). OS was similar for So-Su and Su-So (median 31.5 and 30.2 mo; HR 1.00, 90% CI 0.77-1.30; p=0.5 for superiority). More So-Su patients than Su-So patients reached protocol-defined second-line therapy (57% vs 42%). Overall, adverse event rates were generally similar between the treatment arms. The most frequent any-grade treatment-emergent first-line adverse events were diarrhoea (54%) and hand-foot skin reaction (39%) for sorafenib; and diarrhoea (40%) and fatigue (40%) for sunitinib.
  
  
  CONCLUSIONS
  Total PFS was not superior with So-Su versus Su-So. These results demonstrate that sorafenib followed by sunitinib and vice versa provide similar clinical benefit in mRCC.
  
  
  RESULTS
  We investigated if total progression-free survival (PFS) is improved in patients with advanced/metastatic kidney cancer who are treated with sorafenib and then with sunitinib (So-Su), compared with sunitinib and then sorafenib (Su-So). We found that total PFS was not improved with So-Su compared with Su-So, but both treatment options were similarly effective in patients with advanced/metastatic kidney cancer.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT00732914, www.clinicaltrials.gov.
authors.affiliation: Universitätsklinikum Hamburg-Eppendorf, Hamburg and Caritas-St. Josef Medical Centre, University of Regensburg, Regensburg, Germany. Electronic address: christian.eichelberg@ukr.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Eichelberg
authors.affiliation: Deventer Ziekenhuis, Deventer, The Netherlands.
authors.forename: Walter L
authors.initials: WL
authors.lastname: Vervenne
authors.affiliation: Ludwig Boltzmann Institute for Applied Cancer Research, Centre for Oncology and Haematology, Kaiser Franz Josef-Spital, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: De Santis
authors.affiliation: Gesundheitszentrum Klinikum Amberg, Amberg, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Fischer von Weikersthal
authors.affiliation: Urologische Klinik und Klinik für Hämatologie und Onkologie, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goebell
authors.affiliation: Onkologisches Zentrum Münster, Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Lerchenmüller
authors.affiliation: Urologische Universitätsklinik Greifswald, Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Zimmermann
authors.affiliation: Reinier de Graaf Gasthuis, Delft, The Netherlands.
authors.forename: Monique M E M
authors.initials: MM
authors.lastname: Bos
authors.affiliation: Onkologische Praxis, Hildesheim, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Freier
authors.affiliation: Klinikum Fulda, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Schirrmacher-Memmel
authors.affiliation: Universitätsklinikum Grosshadern, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Staehler
authors.affiliation: Universitätsklinikum Heidelberg, Heidelberg, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Pahernik
authors.affiliation: St. Antonius Ziekenhuis, Nieuwegein, The Netherlands.
authors.forename: Maartje
authors.initials: M
authors.lastname: Los
authors.affiliation: Urologische Universitätsklinik Essen, Essen, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Schenck
authors.affiliation: Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Flörcken
authors.affiliation: Slingeland Ziekenhuis, Doetinchem, The Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Arkel
authors.affiliation: iOMEDICO AG, Freiburg, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Hauswald
authors.affiliation: iOMEDICO AG, Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Indorf
authors.affiliation: ICRC Weyer GmbH, Berlin, Germany.
authors.forename: Dana
authors.initials: D
authors.lastname: Gottstein
authors.affiliation: University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: Maurice S
authors.initials: MS
authors.lastname: Michel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000008:administration & dosage*; D000077157:Sorafenib; D000077210:Sunitinib
chemical_list: D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib
keywords: Renal cell carcinoma; Sequential therapy; Sorafenib; Sunitinib