Clinical development of mTor inhibitors for renal cancer

ABSTRACT

Introduction: 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.

KEYWORDS:

• mTOR inhibitors
• renal cell carcinoma
• advanced disease
• everolimus
• temsirolimus

Article highlights

• mTOR inhibitors are valid options for RCC patients progressing to first line therapy

• Temsirolimus is approved for poor risk RCC

• Everolimus is approved for pretreated RCC

• Combination of lenvatinib and everolimus improved mPFS, mOS and ORR compared with everolimus alone in RCC second line setting

• Second generation mTOR inhibitors (mTORC1 and 2 inhibitors and mTOR/PI3K dual inhibitors) are being developed

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.