title: Efficacy of targeted treatment beyond third-line therapy in metastatic kidney cancer: retrospective analysis from a large-volume cancer center.
abstract: BACKGROUND
  Currently, 7 agents are approved for the first- and second-line therapy for metastatic renal cell carcinoma. In contrast, data supporting their use beyond second line are limited. Here we summarize our experience in patients treated with more than 4 lines of therapy.
  
  
  METHODS
  We retrospectively assessed the outcome of 24 patients treated at our institution with at least 4 lines of therapy. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier estimates.
  
  
  RESULTS
  Median OS from the initiation of first-line therapy for the whole cohort is 64.7 months. Up to 96% of the patients received a tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitor (mTOR-I) within the first 3 lines of treatment. In the fourth or following lines, patients were treated with TKI, mTOR-I, bevacizumab/interferon, or experimental drugs. Seven patients continued treatment with a sixth-line agent; one has been treated up to the ninth line. Sixteen percent of the patients receiving fourth-line therapy and 13% receiving fifth-line therapy experienced a partial remission, which was independent from response to previous therapies. Median OS from fourth and fifth line was 30.8 and 26.2 months, respectively. Median PFS for fourth-line therapy was 5.8 months. No significant difference in PFS was observed for patients with disease that responded or did not respond to first-line therapy.
  
  
  CONCLUSIONS
  Despite the limitations of a retrospective analysis, our study suggests that selected patients benefit from multiple lines of treatment, independent of response to first-line therapy. However, the optimal sequence of treatment with regard to later lines remains to be determined.
authors.affiliation: Department of Medical Oncology, National Center for Tumor Diseases Heidelberg, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Sonia
authors.initials: S
authors.lastname: Vallet
authors.affiliation: Department of Urology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Pahernik
authors.affiliation: Department of Urology, Theresienkrankenhaus, and St. Hedwig-Klinik GmbH, Mannheim, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Höfner
authors.affiliation: Department of Urology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Georgi
authors.initials: G
authors.lastname: Tosev
authors.affiliation: Department of Urology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Hadaschik
authors.affiliation: Department of Urology, Section of Molecular Urooncology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Duensing
authors.affiliation: Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Sedlaczek
authors.affiliation: Department of Urology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Hohenfellner
authors.affiliation: Department of Medical Oncology, National Center for Tumor Diseases Heidelberg, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.affiliation: Department of Medical Oncology, National Center for Tumor Diseases Heidelberg, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: carsten.gruellich@med.uni-heidelberg.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Grüllich
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Metastatic kidney cancer; Multiple lines of treatment; Objective response; Survival; Targeted therapy