Maximising the duration of disease control in metastatic renal cell carcinoma with targeted agents: an expert agreement
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With six targeted agents approved (sorafenib, sunitinib, temsirolimus, bevacizumab [+interferon], everolimus and pazopanib), many patients with metastatic renal cell carcinoma (mRCC) will receive multiple therapies. However, the optimum sequencing approach has not been defined. A group of European experts reviewed available data and shared their clinical experience to compile an expert agreement on the sequential use of targeted agents in mRCC. To date, there are few prospective studies of sequential therapy. The mammalian target of rapamycin (mTOR) inhibitor everolimus was approved for use in patients who failed treatment with inhibitors of vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) based on the results from a Phase III placebo-controlled study; however, until then, the only licensed agents across the spectrum of mRCC were VEGF(R) inhibitors (sorafenib, sunitinib and bevacizumab + interferon), and as such, a large body of evidence has accumulated regarding their use in sequence. Data show that sequential use of VEGF(R) inhibitors may be an effective treatment strategy to achieve prolonged clinical benefit. The optimal place of each targeted agent in the treatment sequence is still unclear, and data from large prospective studies are needed. The Phase III AXIS study of second-line sorafenib vs. axitinib (including post-VEGF(R) inhibitors) has completed, but the data are not yet published; other ongoing studies include the Phase III SWITCH study of sorafenib–sunitinib vs. sunitinib–sorafenib (NCT00732914); the Phase III 404 study of temsirolimus vs. sorafenib post-sunitinib (NCT00474786) and the Phase II RECORD 3 study of sunitinib–everolimus vs. everolimus–sunitinib (NCT00903175). Until additional data are available, consideration of patient response and tolerability to treatment may facilitate current decision-making regarding when to switch and which treatment to switch to in real-life clinical practice.
KeywordsRCC Sequence Renal cell carcinoma Tyrosine kinase inhibitor Sorafenib Sunitinib Pazopanib Bevacizumab Everolimus Temsirolimus
The European expert meeting was supported by Bayer HealthCare Pharmaceuticals. The authors are grateful to 7.4 Limited for providing editorial support on this manuscript, with financial support from Bayer HealthCare Pharmaceuticals.
Conflicts of interest
GT and DB have no additional conflicts of interest to declare. CP has received research grants from Bayer HealthCare and Novartis Pharma and has acted as a paid consultant or speaker for Bayer HealthCare, Pfizer Oncology, Hoffmann-La Roche, Wyeth Pharmaceuticals, Novartis Pharma and GlaxoSmithKline. CL has received research grants from Hoffmann-LaRoche and Schering-Plough and has acted as a paid speaker for Bayer HealthCare, Amgen and Vifor. KP has served on advisory boards for Novartis, Roche and Bayer HealthCare. AA has received honoraria for participating in advisory boards organised by Bayer HealthCare, Pfizer and GlaxoSmithKline. JPM has acted as a paid consultant or speaker for Bayer HealthCare, Pfizer Oncology, Hoffmann-La Roche, Wyeth Pharmaceuticals, Novartis Pharma and GlaxoSmithKline. TP has received research grants from Novartis, GlaxoSmithKline, Astra Zeneca and Pfizer and has acted as a paid consultant or speaker for Pfizer, Astra Zeneca, Novartis and GlaxoSmithKline. MDS has acted as a consultant, received honoraria or served on advisory boards for Novartis, GlaxoSmithKline, Pierre-Fabre Oncology, Roche, Amgen, Dendreon, Janssen Cilag, Bayer HealthCare, Eli Lilly, Sanofi Aventis and Pfizer.
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