title: The role of mTOR inhibition as second-line therapy in metastatic renal carcinoma: clinical evidence and current challenges.
abstract: 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.
authors.affiliation: a Servicio de Oncología Médica , Hospital Clínico San Carlos , Madrid , Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: González-Larriba
authors.affiliation: b Servicio de Oncología Médica , Hospital de la Santa Creu i Sant Pau , Barcelona , Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Maroto
authors.affiliation: c Sección de Oncología Médica, Hospital Universitario Virgen del Rocío , Sevilla , Spain.|d Laboratorio de Terapias Avanzadas y Biomarcadores en Oncología , Instituto de Biomedicina de Sevilla , Sevilla , Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Durán
authors.affiliation: e Servicio de Oncología Médica , Hospital Clínico Universitario Lozano Blesa , Zaragoza , Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Lambea
authors.affiliation: f Novartis Oncology , Barcelona , Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Flores
authors.affiliation: g Servicio de Oncología Médica , Hospital 12 de Octubre , Madrid , Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
mesh_terms: D000813:Anilides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis; D000077594:Nivolumab; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000813:Anilides; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C558660:cabozantinib; D000077594:Nivolumab; D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases
keywords: adverse event; everolimus; mTOR; real-world clinical practice; renal cancer; temsirolimus