title: No Significant Correlation of Clinical Outcomes Between First- and Second-line Tyrosine Kinase Inhibitors in Patients with Metastatic Renal Cell Carcinoma.
abstract: OBJECTIVE
  To identify patients with metastatic renal cell carcinoma (mRCC) who received tyrosine kinase inhibitors (TKIs) in both first- and second-line settings in order to investigate the association of oncological outcomes between the two lines of therapy. Patients with Methods: The study included 76 consecutive patients with mRCC treated with second-line TKI therapy after the failure of first-line TKI therapy. The association of oncological outcomes between first- and second-line therapies was analyzed in these 76 patients.
  
  
  RESULTS
  In this series, the objective response rates (ORRs) to first- and second-line TKI therapies were 10.5% and 25.0%, respectively. The ORR to second-line TKI therapy was not significantly different among patients achieving a complete or partial response, stable disease and progressive disease to first-line TKI therapy (37.5%, 21.6% and 29.4%, respectively; p=0.34). The median durations of progression-free survival (PFS) with first- and second-line TKI therapies were 7.9 and 8.1 months, respectively, and there was no significant correlation between them (p=0.78). Out of the examined factors, the pre-treatment C-reactive protein level, number of metastatic sites and Memorial Sloan-Kettering Cancer Center risk classification model, but not the response to first-line TKI therapy, were independently associated with PFS on second-line TKI therapy, based on multivariate analysis.
  
  
  CONCLUSIONS
  The clinical response to second-line TKI therapy is not dependent on that to first-line TKI therapy in patients with mRCC; therefore, it may not be necessary to switch to an alternative agent with a mechanism different from TKIs as second-line therapy, even if patients do not respond to first-line TKI therapy.
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan hideakimiyake@hotmail.com.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Harada
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D002097:C-Reactive Protein; D058570:TOR Serine-Threonine Kinases
keywords: Tyrosine kinase inhibitor; first-line; metastatic renal cell carcinoma; objective response; progression-free survival; second-line