Clinical development of mTor inhibitors for renal cancer

Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 90-95% of neoplasms arising from the kidney. In the last 10 years, clinical trials have established multitargeted tyrosine kinase inhibitors (TKIs) as the standard first-line treatment in patients with metastatic disease. Multiple agents are now available for treatment in subsequent lines.The mammalian target of rapamycin (mTOR) inhibitors (e.g., everolimus alone or with lenvatinib) are among the most effective options. Areas covered: This paper provides a complete and updated overview on mTOR inhibitors for the treatment of advanced RCC. The authors revised the results of the most recent completed clinical trials and provided information about ongoing trials. Expert opinion: mTOR pathway still represents an important driver for RCC management. Combination of everolimus and lenvatinib is considered a category 1 choice with cabozantinib and nivolumab for subsequent therapy in metastatic RCC according to NCCN guidelines v2.2017. These three treatments (levantinib/everolimus, cabozantinib, and nivolumab) all resulted in a superior efficacy compared to everolimus alone. Moreover, mTOR inhibitors, and in particular temsirolimus for poor risk patients, are available choices for treatment in non-clear cell carcinomas together with TKIs.

Expert opinion on investigational drugs. 2017 Sep 27 [Epub ahead of print]

Michele Ghidini, Fausto Petrelli, Antonio Ghidini, Gianluca Tomasello, Jens Claus Hahne, Rodolfo Passalacqua, Sandro Barni

a Oncology Unit, Oncology Department , ASST Ospedale di Cremona , Viale Concordia 1, 26100 , Cremona , Italy., b Oncology Unit, Oncology Department , ASST Bergamo Ovest , Piazzale Ospedale 1, 24047 , Treviglio (BG) , Italy., c Medical Oncology , Casa di Cura Igea , Via Marcona 69, 20144 Milano , Italy., d Laboratory of Gastrointestinal Cancer Biology and Genomics, Division of Molecular Pathology , The Institute of Cancer Research , 15 Cotswold Road, Sutton , Surrey , SM25NG , UK .