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

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.

Expert review of anticancer therapy. 2017 Jan 20 [Epub ahead of print]

José Luis González-Larriba, Pablo Maroto, Ignacio Durán, Julio Lambea, Luis Flores, Daniel Castellano, Changing Group

a Servicio de Oncología Médica , Hospital Clínico San Carlos , Madrid , Spain., b Servicio de Oncología Médica , Hospital de la Santa Creu i Sant Pau , Barcelona , Spain., c Sección de Oncología Médica , Hospital Universitario Virgen del Rocío , Sevilla , Spain., e Servicio de Oncología Médica , Hospital Clínico Universitario Lozano Blesa , Zaragoza , Spain., f Novartis Oncology , Barcelona , Spain., g Servicio de Oncología Médica , Hospital 12 de Octubre , Madrid , Spain.