Systemic Therapy for Metastatic Non-Clear Cell Renal Carcinoma

Renal cell carcinoma (RCC) comprises 2-3% of all malignancies. Approximately 90% of renal tumors are RCCs, and 15% of these are non-clear cell tumors, which include papillary, chromophobe, Bellini duct (collecting duct) and sarcomatoid tumors. Antiangiogenic agents (sorafenib, sunitinib, pazopanib, temsirolimus, or bevacizumab), have not been specifically evaluated in phase III trials in patients with nonclear cell tumors. Therefore, their efficacy is unclear in the treatment of non-clear cell renal carcinomas. In a subset analysis of a randomized phase III trial, patients with non-clear cell and clear cell advanced RCCs, treated with temsirolimus, demonstrated comparable median overall and progression-free survival. In addition, temsirolimus resulted in a superior clinical benefit rate compared with interferon-alfa, regardless of tumor histology. Patients with metastatic papillary and chromophobe RCCs may have prolonged progression-free survival from sunitinib and sorafenib, although clinical responses remain overall low. Therefore, although there are some evidences supporting the use of these agents in patients with non-clear cell RCCs, additional prospective trials with these agents are needed to further clarify their use in these histologic subtypes. This review article focuses on all these options for non-clear cell advanced RCC.