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

Eur Urol. 2015 Nov;68(5):837-47. doi: 10.1016/j.eururo.2015.04.017. Epub 2015 May 4.


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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / secondary
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / secondary
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / secondary
  • Disease-Free Survival
  • Female
  • Humans
  • Indoles / administration & dosage*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / secondary
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Lymph Nodes / pathology
  • Male
  • Middle Aged
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Phenylurea Compounds / administration & dosage*
  • Proportional Hazards Models
  • Pyrroles / administration & dosage*
  • Sorafenib
  • Sunitinib


  • Indoles
  • Phenylurea Compounds
  • Pyrroles
  • Niacinamide
  • Sorafenib
  • Sunitinib

Associated data

  • ClinicalTrials.gov/NCT00732914