title: Expert Recommendations for First-Line Management of Metastatic Renal Cell Carcinoma in Special Subpopulations.
abstract: The availability of agents targeting the vascular endothelial growth factor or mammalian target of rapamycin [mTOR] pathways has provided new treatment options for patients with metastatic renal cell carcinoma (RCC). Based on the results of pivotal randomized clinical trials, specific recommendations have been established for management of these patients in first- and second-line settings. However, certain subgroups of patients may be excluded or under-represented in clinical trials, including patients with poor performance status, brain metastases, and cardiac or renal comorbidities, elderly patients, and those with non-clear cell histology. For these subpopulations, management recommendations have emerged from expanded access programs (EAPs), small phase II studies, retrospective analysis of clinical data, and expert opinion. This paper describes recommendations from an expert panel for the treatment of metastatic RCC in these subpopulations. The efficacy of targeted agents appears to be inferior in these patient subgroups relative to the general RCC population. Tyrosine kinase inhibitors (TKIs) and mTOR inhibitors can be administered safely to elderly patients and those with poor performance status, although dose and schedule modifications are often needed, and close monitoring and management of adverse events is essential. In addition to local surgical treatment and radiotherapy for brain metastases, systemic treatment with a TKI should be offered as part of multidisciplinary care.While there are currently no data from randomized trials, sunitinib has the greatest body of evidence, and it should be considered the first choice in patients with a good prognosis. Patients with an acute cardiac event within the previous 6 months, New York Heart Association grade III heart failure, or uncontrolled high blood pressure should not be treated with TKIs. In patients with mild or moderate renal failure, there are no contraindications to TKI treatment. TKIs can be administered to patients undergoing dialysis, but other, less nephrotoxic agents and other alternatives should always be considered.In managing RCC among patients with non-clear cell histology, sunitinib seems to be more effective than everolimus for the papillary subtype, but there are no clear data to guide treatment for other subtypes. In conclusion, individualized treatment approaches are needed to manage RCC in subpopulations that are underrepresented in registration clinical trials.
authors.affiliation: Department of Medical Oncology, Hospital Clínico Universitario San Carlos, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Puente
authors.affiliation: Department of Medical Oncology, Instituto Catalán de Oncología (ICO), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: García Del Muro
authors.affiliation: Department of Medical Oncology, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Pinto
authors.affiliation: Department of Medical Oncology, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Láinez
authors.affiliation: Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Esteban
authors.affiliation: Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: José Ángel
authors.initials: JÁ
authors.lastname: Arranz
authors.affiliation: Department of Medical Oncology, Hospital Universitari Parc Taulí, Sabadell, Barcelona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Gallardo
authors.affiliation: Department of Medical Oncology, Hospital Reina Sofía, Córdoba, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Méndez
authors.affiliation: Department of Medical Oncology, Hospital Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Maroto
authors.affiliation: Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Grande
authors.affiliation: Department of Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology, Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035, Barcelona, Spain. crisuarez08@gmail.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Suárez
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents