• Christian Eichelberg, Walter L Vervenne, Maria De Santis, Fischer von Weikersthal Ludwig L Gesundheitszentrum Klinikum Amberg, Amberg, Germany., Peter J Goebell, Christian Lerchenmüller, Uwe Zimmermann, Monique M E M Bos, Werner Freier, Silke Schirrmacher-Memmel, Michael Staehler, Sascha Pahernik, Maartje Los, Marcus Schenck, Anne Flörcken, Cornelis van Arkel, Kirsten Hauswald, Martin Indorf, Dana Gottstein, and Maurice S Michel.
• Universitätsklinikum Hamburg-Eppendorf, Hamburg and Caritas-St. Josef Medical Centre, University of Regensburg, Regensburg, Germany. Electronic address: christian.eichelberg@ukr.de.
• Eur. Urol. 2015 Nov 1; 68 (5): 837-47.

BackgroundUnderstanding how to sequence targeted therapies for metastatic renal cell carcinoma (mRCC) is important for maximisation of clinical benefit.ObjectivesTo 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.Design, Setting, And ParticipantsThe 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).InterventionPatients 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).Outcome Measurements And Statistical AnalysisThe 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.Results And LimitationsIn 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.ConclusionsTotal 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.Patient SummaryWe 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.Trial RegistrationClinicalTrials.gov identifier NCT00732914, www.clinicaltrials.gov.Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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