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
Christian Eichelberg, Walter L Vervenne, Maria De Santis, Ludwig Fischer von Weikersthal, 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, Maurice S Michel, Christian Eichelberg, Walter L Vervenne, Maria De Santis, Ludwig Fischer von Weikersthal, 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, Maurice S Michel
Abstract
Background: Understanding how to sequence targeted therapies for metastatic renal cell carcinoma (mRCC) is important for maximisation of clinical benefit.
Objectives: 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.
Design, setting, and participants: 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).
Intervention: 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).
Outcome measurements and statistical analysis: 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.
Results and limitations: 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.
Patient summary: 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.
Trial registration: ClinicalTrials.gov identifier NCT00732914, www.clinicaltrials.gov.
Keywords: Renal cell carcinoma; Sequential therapy; Sorafenib; Sunitinib.
Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Source: PubMed