As Dr. Powles noted, the recently updated European Guidelines  recommend pazopanib or sunitinib as first line therapy and now recommend cabozantinib or nivolumab in the secondary setting for VEGF resistant disease, after the head to head comparison of nivolumab vs everolimus (OS, HR 0.73, 95%CI 0.57-0.93) . Other important findings from this study are that patient reported quality of life was much improved for those receiving nivolumab compared to everolimus. As Dr. Powles highlighted, we have delineated different locations of the cancer immunity cycle, allowing treatment with IL-2 (immune “priming and activation”), atezolizumab (anti-PD-L1) and bevacizumab (VEGF inhibitor) + IFN-alpha-2a.
Combination therapy trials are also being rigorously tested, notably a phase Ib study in first-line mRCC assessing atezolizumab + bevacizumab, which showed anti-tumor activity and a tolerant safety profile. Dr. Powles also highlighted the IMmotion150 phase II trial for patients with treatment naïve, locally advanced or mRCC (n=305) randomized 1:1:1 to receive atezolizumab + bevacizumab or atezolizumab or sunitinib with coprimary endpoints of progression free survival (PFS) and PD-L1 positivity. In the intention to treat analysis, there was no difference in OS between the three groups, however in the PD-L1 positive patients (≥1% expression) there was a statistical trend towards significantly improved outcomes for patients receiving atezolizumab + bevacizumab (median OS 14.7 months) vs sunitinib (median OS 7.8 months) (HR 0.64, 95%CI 0.38-1.08). Other combination studies in the mRCC setting are looking at pembrolizumab + axitinib and nivolumab + ipilimumab.
Dr. Powles summarized his talk by stating that we are currently in an exciting time for treating mRCC patients, with immune therapy now established in the second line. Furthermore, patients are living longer and feeling better with new treatment regimens. Future directions and challenges remain, including “picking the winners” of combination therapy, developing biomarkers to help with stratifying care, and considering triplet combination therapy to enable durable responses >50%.
1. Powles T, Staehler M, Ljungberg B, et al. European Association of Urology Guidelines for Clear Cell Renal Cancers that are resistant to vascular endothelial growth factor receptor-targeted therapy. Eur Urol 2016;70(5):705-706.
2. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015;373(19):1803-1813.
Speaker: Thomas Powles, Barts Cancer Centre, London, UK
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto
at the #EAU17 - March 24-28, 2017- London, England