NEW YORK (Reuters Health) - New guidelines from the European Association of Urology recommend using the experimental drugs nivolumab and cabozantinib if one or more lines of vascular endothelial growth factor (VEGF)-targeted therapy fail in patients with clear cell renal cancer.
Agents that target the VEGF receptor have improved outcomes of metastatic clear cell renal cell carcinoma, Dr. Thomas Powles from The Royal Free NHS Trust and Barts Cancer Institute, Queen Mary University of London, and colleagues note in European Urology, online October 24. But outcomes remain poor, they add, and the optimal therapy for patients who don't respond to VEGF-targeted therapy remains uncertain.
Based on recently completed randomized controlled trials, Dr. Powles and colleagues from the European Association of Urology (EAU) revised the guidelines for clear cell renal cancer patients who fail VEGF-targeted therapy.
Nivolumab, a monoclonal antibody that targets the programmed cell death 1 (PD1) immune checkpoint, provides overall survival superior to that of everolimus, the previously recommended treatment for these patients.
Cabozantinib, a multi-tyrosine kinase inhibitor (TKI) of MET, AXL, and VEGF, delays progression or death, compared with everolimus, in these patients, the authors report. So far, only interim results are available for overall survival.
Accordingly, the EAU now recommends nivolumab first and cabozantinib second for patients who don't respond to sunitinib or pazopanib. Axitinib, whose results are also superior to everolimus, is also recommended, though there is no overall survival advantage.
Patients who fail nivolumab should receive a trial of cabozantinib, and those who fail cabozantinib or axitinib should receive a trial of nivolumab, the authors advise.
The guidelines recommend drugs not previously given, especially nivolumab or cabozantinib, as fourth-line therapy.
"Both everolimus and sorafenib have been outperformed by other agents in VEGF-refractory disease and should not be routine standard of care in pure VEGF-refractory disease," the authors conclude. "It is not currently possible to determine therapy based on baseline characteristics or biomarker expression for any of the drugs described."
Neither nivolumab nor cabozantinib is included in the current National Comprehensive Cancer Network (NCCN) guidelines for patients who don't respond to first-line therapy. NCCN continues to list everolimus and axitinib as category 1 treatments after TKI therapy and axitinib, sorafenib, sunitinib, and pazopanib as category 1 treatments after cytokine therapy.
According to a spokesperson, the American Urological Association guidelines "are focused only on localized disease," not metastatic kidney cancer. "Our Guidelines would not apply here," the spokesperson told Reuters Health by email.
Dr. Powles did not respond to a request for comments.
Eur Urol 2015.