title: Vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) rechallenge for patients with metastatic renal cell carcinoma after treatment failure using both VEGFR-TKI and mTOR inhibitor.
abstract: OBJECTIVE
  To assess the efficacy of vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) rechallenge for metastatic renal cell carcinoma (mRCC) patients and to identify predictive factors for increased progression-free survival (PFS) or overall survival (OS).
  
  
  METHODS
  The clinicopathological features, outcomes, and prognostic factors of mRCC patients who were treated with VEGFR-TKI after treatment failure using both VEGFR-TKIs and mTOR inhibitors (mTORi) were reviewed.
  
  
  RESULTS
  A total of 29 eligible patients were included. Five (17 %) patients achieved partial response (PR) with a median response duration of 9.5 months (95 % CI 5.7-13.4 months), and additional 16 patients (55 %) achieved stable disease. With a median follow-up period of 19.2 months (95 % CI 18.9-19.6 months), the median PFS and OS were 3.0 months (95 % CI 1.1-4.9 months) and 4.9 months (95 % CI 2.9-6.8 months), respectively. In univariate analysis, the best response to first-line VEGFR-TKI (PR vs. non-PR, p < 0.001) and time to rechallenge (TTR, ≤12 months vs. between 12 and 24 months vs. >24 months, p = 0.005) were identified as predictive factors for longer PFS on VEGFR-TKI rechallenge. In addition, an MSKCC risk group (intermediate- vs. poor-risk group, p = 0.027), better response at first-line VEGFR-TKI (PR vs. non-PR, p = 0.003), and TTR (≤12 months vs. between 12 and 24 months vs. >24 months, p = 0.026) were identified as prognostic factors for longer OS.
  
  
  CONCLUSIONS
  VEGFR-TKI rechallenge may be a viable option for select metastatic RCC patients who fail both VEGFR-TKI and mTORi therapies.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
authors.forename: Inkeun
authors.initials: I
authors.lastname: Park
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Ahn
authors.forename: Dae-Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
authors.forename: Dalsan
authors.initials: D
authors.lastname: You
authors.forename: In Gab
authors.initials: IG
authors.lastname: Jeong
authors.forename: Cheryn
authors.initials: C
authors.lastname: Song
authors.forename: Bumsik
authors.initials: B
authors.lastname: Hong
authors.forename: Jun Hyuk
authors.initials: JH
authors.lastname: Hong
authors.forename: Hanjong
authors.initials: H
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus