title: Evaluation of second-line and subsequent targeted therapies in metastatic renal cell cancer (mRCC) patients treated with first-line cediranib.
abstract: BACKGROUND
  Pivotal phase III trials have positioned angiogenesis inhibitors as first-line therapy for the management of most advanced or metastatic renal cell carcinomas (mRCC). Approaches to second-line therapy, however, remain more controversial with respect to drug selection and drug sequencing.
  
  
  METHODS
  In this study we evaluated mRCC patients who were initially treated on the first-line National Cancer Institute (NCI) trial with the highly potent vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI), cediranib, to determine the efficacy and tolerability of subsequent therapies.
  
  
  RESULTS
  Twenty-eight (65.1%) of the 43 patients enrolled on the first-line cediranib trial were known to receive second-line therapy, most commonly sunitinib (n = 21), with 4 (14%), 2 (7%) and 1 (3%) patients receiving temsirolimus, sorafenib, and interleukin, respectively. Of these, 14 (50%) went on to have 3 or more lines of therapy. The progression-free survival (PFS) proportion (PFS) at 1 year from starting second line was 30% (14.5%-47.9%). Longer duration of first-line cediranib treatment was modestly associated with longer duration of second-line treatment (Spearman rho 0.26). Patients who discontinued cediranib for toxicity were less likely to receive second-line sunitinib.
  
  
  CONCLUSIONS
  In this real world evaluation, sequential use of TKIs for the management of mRCC was common. PFS with sequential TKIs was similar to observed and published results for any second-line therapy. Prior toxicity affected treatment patterns and the frequent use of at least 3 lines of therapy underscores the need for prospective sequencing trials in this disease.
authors.affiliation: Princess Margaret Cancer Centre, Toronto, ON;
authors.forename: Suzanne
authors.initials: S
authors.lastname: Richter
authors.affiliation: Princess Margaret Cancer Centre, Toronto, ON;
authors.forename: Jo-An
authors.initials: JA
authors.lastname: Seah
authors.affiliation: McMaster University, Hamilton, ON;
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.affiliation: Austin Health, Ludwig Institute for Cancer Research, Melbourne, Australia;
authors.forename: Hui K
authors.initials: HK
authors.lastname: Gan
authors.affiliation: London Region Cancer Program, Western University, London, ON;
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Mackenzie
authors.affiliation: Juravinski Cancer Centre, McMaster University, Hamilton, ON;
authors.forename: Sebastien J
authors.initials: SJ
authors.lastname: Hotte
authors.affiliation: Juravinski Cancer Centre, McMaster University, Hamilton, ON;
authors.forename: Som D
authors.initials: SD
authors.lastname: Mukherjee
authors.affiliation: BC Cancer Agency, University of British Columbia, Vancouver, BC;
authors.forename: Nevin
authors.initials: N
authors.lastname: Murray
authors.affiliation: BC Cancer Agency, University of British Columbia, Vancouver, BC;
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.affiliation: Tom Baker Cancer Centre, University of Alberta, Calgary, AB;
authors.forename: Daniel
authors.initials: D
authors.lastname: Heng
authors.affiliation: Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON;
authors.forename: Masoom A
authors.initials: MA
authors.lastname: Haider
authors.affiliation: Princess Margaret Cancer Centre, Toronto, ON;
authors.forename: Robert
authors.initials: R
authors.lastname: Halford
authors.affiliation: Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD.
authors.forename: S Percy
authors.initials: SP
authors.lastname: Ivy
authors.affiliation: Princess Margaret Cancer Centre, Toronto, ON;
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
authors.affiliation: Princess Margaret Cancer Centre, Toronto, ON;
authors.forename: Srikala S
authors.initials: SS
authors.lastname: Sridhar