Current and future strategies in nonclear-cell metastatic renal cell carcinoma

Purpose of review Therapeutic options for patients with metastatic nonclear-cell renal cell carcinoma (non-ccRCC) are limited and display minimum benefit. Conducting clinical trials in these rare and heterogeneous diseases without identified key biological drivers is a challenge for drug development. A growing body of prospective dedicated clinical trials and large molecular characterization initiatives are raising new expectations in non-ccRCC. Recent findings The first randomized phase II study in non-ccRCC failed to demonstrate the benefit of everolimus over sunitinib in first-line setting, although this study was small and was not supposed to draw final conclusions. Single-arm phase II trials have reported the results of sunitinib or everolimus in the papillary. The potential role of a sunitinib'gemcitabine combination has been investigated in RCC with sarcomatoid features. In parallel, the molecular characterization of non-ccRCC has been initiated, highlighting the heterogeneity of the distinct subtypes. Summary Current efforts to develop clinical trials in non-ccRCC have provided preliminary results with approved agents. The molecular characterization programs have not yet translated into clinical meaningful results, but MET proto-oncogene inhibition holds promises in the population of papillary RCC. Non-ccRCC management raises the challenge of structuring networks to optimize pathological diagnosis, target identification, and for dedicated clinical trials design.