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

详细信息    查看全文

• 作者：Christian Eichelberg^a ; ^{christian.eichelberg@ukr.de" class="auth_mail" title="E-mail the corresponding author} ; Walter L. Vervenne^b ; Maria De Santis^c ; Ludwig Fischer von Weikersthal^d ; Peter J. Goebell^e ; Christian Lerchenmü ; ller^f ; Uwe Zimmermann^g ; Monique M.E.M. Bos^h ; Werner Freierⁱ ; Silke Schirrmacher-Memmel^j ; Michael Staehler^k ; Sascha Pahernik^l ; Maartje Los^m ; Marcus Schenckⁿ ; Anne Flö ; rcken^o ; Cornelis van Arkel^p ; Kirsten Hauswald^q ; Martin Indorf^q ; Dana Gottstein^r ; Maurice S. Michel^s
• 关键词：Renal cell carcinoma ; Sequential therapy ; Sorafenib ; Sunitinib
• 刊名：European Urology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：68
• 期：5
• 页码：837-847
• 全文大小：1374 K

文摘

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 400 mg twice daily followed, on progression or intolerable toxicity, by sunitinib 50 mg 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