title: Progression-free survival as a predictor of overall survival in metastatic renal cell carcinoma treated with contemporary targeted therapy.
abstract: BACKGROUND
  The majority of metastatic renal cell carcinoma (mRCC) clinical trials that examined targeted agents used progression-free survival (PFS) as the primary endpoint. Whether PFS can be used as a predictor of overall survival (OS) is unknown.
  
  
  METHODS
  Patients from 12 cancer centers who received targeted therapy for mRCC were identified. Landmark analyses for progression at 3 months and 6 months after drug initiation were performed to minimize lead-time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS.
  
  
  RESULTS
  In total, 1158 patients were included. The median follow-up was 30.6 months, the median age was 60 years, and the median Karnofsky performance status was 80%. For the entire cohort, the median PFS was 7.6 months, and the median OS was 19.7 months. In the landmark analysis, the median OS for patients who progressed at 3 months was 7.8 months compared with 23.6 months for patients who did not progress (log-rank test; P < .0001). Similarly, for patients who progressed at 6 months, the median OS was 8.6 months compared with 26 months for patients who did not progress (P < .0001). Compared with those who did not progress, for the patients who progressed at 3 months and at 6 months, the hazard ratios for death adjusted for adverse prognostic factors were 3.05 (95% confidence interval, 2.42-3.84) and 2.96 (95% confidence interval, 2.39-3.67), respectively. Similar results were demonstrated with landmark analyses at 9 months and at 12 months and in the bootstrap validation. Kendall tau rank correlation and a Fleischer model demonstrated a statistically significant dependent correlation.
  
  
  CONCLUSIONS
  PFS at 3 months and at 6 months predicted OS, and the current results indicated that PFS may be a meaningful intermediate endpoint for OS in patients with mRCC who receive treatment with novel agents.
authors.affiliation: Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada. daniel.heng@albertahealthservices.ca
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.forename: Georg A
authors.initials: GA
authors.lastname: Bjarnason
authors.forename: Ulka
authors.initials: U
authors.lastname: Vaishampayan
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Knox
authors.forename: Frede
authors.initials: F
authors.lastname: Donskov
authors.forename: Lori
authors.initials: L
authors.lastname: Wood
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000401:mortality* / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models