Changing paradigm of immunooncology in advanced kidney cancer: nivolumab and ipilimumab combination in the first line therapy

Until now selection of the 1st line therapy for advanced clear-cell renal cell carcinoma was determined by patients distribution into favorable/ intermediate or poor prognosis groups. In the favorable/ intermediate prognostic groups agents of choice included antiangiogenic substances such as bevacizumab (in combination with interferon-alpha), sunitinib, andpazopanib, which had demonstrated only progression-free survival benefit comparing with interferon-alpha in registration studies; in the poor prognosis group the only treatment option was mammalian target of rapamycin inhibitor temsirolimus which had improved overall survival comparing with interferon-alpha. However about 75 % of advanced renal cell carcinoma patients have intermediate or poor prognosis. Only 2 randomized trials investigated systemic therapy in this cohort of patients, CABOSUN and CheckMate 214. The results of the randomized phase III study CheckMate 214 have demonstrated a significant advantage of overall survival and objective response rate in previously untreated patients of intermediate/poor prognostic groups who were randomizedfor combined immunotherapy with nivolumab and ipilimumab comparing with sunitinib independently of PD-L1 expression level. Owing to the achieved data combined immunotherapy became a new standard of the first-line therapy in advanced renal-cell carcinoma patients with intermediate and poor prognosis.