The role of mTOR inhibition as second-line therapy in metastatic renal carcinoma: clinical evidence and current challenges

ABSTRACT

Introduction: Sequential treatment with targeted agents is the standard of care for patients with metastatic renal cell carcinoma (mRCC). Although first-line therapy with tyrosine kinase inhibitors (TKIs) is recommended for most patients, eventually all patients become resistant to them. Therefore, optimal selection of second-line therapy is crucial.

Areas covered: We have reviewed the recent literature through pubmed search and recent congress presentations to briefly describe the clinical evidence for mTOR inhibition as a valid strategy in the treatment of mRCC after progression during anti-VEGFR therapy. In addition, we outline the management of adverse events associated with these agents, highlighting the importance of switching to an alternative mechanism of action to overcome resistance to TKI and to decrease cumulative toxicity associated with sequential treatments of the same type.

Expert commentary: The choice of subsequent therapy after progression to first-line is not clear. Although the new drugs cabozantinib and nivolumab have shown to be superior that everolimus, still it is unknown which patients may benefit from these therapies in second-line, so treatment should be personalized to each patient and should consider approaches with different mechanisms of action.

KEYWORDS:

• mTOR
• everolimus
• temsirolimus
• adverse event
• real-world clinical practice
• renal cancer

Acknowledgements

The authors wish to thank Dr. Fernando Sánchez Barbero and Nature Publishing Group Iberoamérica for help in the preparation of this manuscript.

The Changing Group is comprised of Urbano Anido ([email protected]), Laura Basterrechea ([email protected]), Oriol Casanovas ([email protected]), Daniel Castellano ([email protected]), Isabel Chirivella ([email protected]), Miguel Ángel Climent ([email protected]), Ignacio Durán ([email protected]), Luis Flores ([email protected]), Enrique Gallardo ([email protected]), Rosa García ([email protected]), Julio Lambea ([email protected]), José Luis González-Larriba ([email protected]), Marta Guix ([email protected]), Nuria Laínez ([email protected]), Almudena Martín Marino ([email protected]), Pablo Maroto ([email protected]), Álvaro Montesa ([email protected]), Alvaro Pinto ([email protected]), Javier Puente ([email protected]), Gustavo Rubio Romero ([email protected]), Cristina Suárez ([email protected]) and Juan A. Virizuela ([email protected]).

Declaration of interest

P Maroto declares that has been economically compensated with his assistance to advisory boards from Novartis, Pfizer, and GlaxoSmithKline. I Durán declares that has been economically compensated with his assistance to advisory boards from Roche-Genentech, Bristol-Myers Squibb, Exelisis, and Novartis. J Lambea declares that has been economically compensated with his assistance to advisory boards and conferences from Novartis and Pfizer. L Flores works in Novartis Oncology. The Changing Group is funded by Novartis Oncology. The authors have no other 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 apart from those disclosed.

Additional information

Funding

This paper has been funded by Novartis Oncology, Barcelona, Spain.