Manuela Schmidinger, MD

Are we seeing a great change in paradigm in the first-line treatment of metastatic renal cell carcinoma? Vascular endothelial growth factor (VEGF) has been recognized as one of the major drivers of clear-cell metastatic renal cell carcinoma and, more than a decade ago, VEGF inhibitors were established as the new standard of care in metastatic renal cell carcinoma. ESMO treatment guidelines recommend VEGF inhibitors in first-line treatment for patients with favorable or intermediate risk. These agents received approval based on PFS and ORR, and not on OS. OS would have confounded data — for instance, see the final OS analysis of sunitinib vs. interferon alpha by Motzer and colleagues; the CALGB 90206 trial on bevacizumab (Avastin, Genentech) plus interferon vs. interferon monotherapy by Rini and colleagues; bevacizumab with interferon alpha-2a vs. placebo and interferon alpha-2a in the AVOREN trial; and pazopanib (Votrient, Novartis) vs. placebo phase 3 data from Sternberg and colleagues — because patients could either cross over or have access to a VEGF inhibitor after treatment failure.