title: Controversies in renal cell carcinoma: treatment choice after progression on vascular endothelial growth factor-targeted therapy.
abstract: The mammalian target of rapamycin inhibitor (mTORI) everolimus and the tyrosine kinase inhibitor (TKI) axitinib are the only two post-first-line treatment options for metastatic renal cell carcinoma (mRCC) licensed at present. Extrapolation of robust phase III studies suggests that median progression-free survival (PFS) is similar between agents. This presents a dilemma for the physician planning treatment for their patients with mRCC: should they be treated with a TKI-mTORI or a TKI-TKI sequence? The lack of direct comparison between axitinib and everolimus leaves the clinician without clear guidance on the optimal choice in second-line therapy. In phase III studies, both post first-line everolimus and axitinib have been shown to delay disease progression; however, cumulative toxicity with sequential use of TKIs may result in more treatment interruptions or dose reductions or increased likelihood of adverse events. While everolimus exerts a tolerability advantage, axitinib is associated with higher response rate and a similar PFS benefit. Proven superiority cannot be used to guide treatment sequence selection in mRCC. Instead, therapeutic planning requires us to take a long-term view of our patient's treatment that includes quality of life and a balance between symptom control, adverse event management and avoidance of unnecessary drug interruptions or dose reductions. In the absence of curative therapies, sustaining a patient's quality of life is a major goal throughout the course of treatment and choosing a second-line agent that is able to adequately achieve this by limiting adverse events should be a priority.
authors.affiliation: Centro Integral Oncológico Clara Campal and START Madrid, Madrid, Spain. Electronic address: emiliano.calvo@start.stoh.com.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Calvo
authors.affiliation: Clinic for Hematology, Hemostasis, Oncology and Stemcell Transplantation, Medical School Hannover, Germany.
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
authors.affiliation: University Hospital del Mar, Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077784:Axitinib; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D000068338:Everolimus; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007191:Indazoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D058990:Molecular Targeted Therapy / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011788:Quality of Life; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068338:Everolimus; D000077784:Axitinib; D020123:Sirolimus
keywords: Quality of life; Renal cell carcinoma; Second-line; Sequencing; Treatment planning