title: Relationship between 6- and 9-month progression-free survival and overall survival in patients with metastatic urothelial cancer treated with first-line cisplatin-based chemotherapy.
abstract: BACKGROUND
  Use of progression-free survival (PFS) as a clinical trial endpoint in first-line treatment of patients with metastatic urothelial carcinoma (UC) is attractive, but would be enhanced by establishing a correlation between PFS and overall survival (OS).
  
  
  METHODS
  Data was pooled from 7 phase 2 and 3 trials evaluating cisplatin-based chemotherapy in metastatic UC. An independent cohort of patients enrolled on a phase 3 trial was used for external validation. Landmark analyses for progression at 6 and 9 months after treatment initiation were performed to minimize lead-time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS.
  
  
  RESULTS
  A total of 364 patients were included in the initial cohort. The median PFS was 8.21 months (95% confidence interval = 7.43, 8.39) and the median OS was 13.50 months (95% confidence interval = 11.80, 15.67). In the landmark analysis, the median OS for patients who progressed at 6 months was 3.87 months compared with 15.06 months for those patients who did not progress (P < .0001) and the median OS for patients who progressed at 9 months was 5.65 months compared with 21.39 months for those patients who did not progress (P < .0001). A Fleischer model demonstrated a statistically significant dependent correlation between PFS and OS. The findings were externally validated in an independent cohort.
  
  
  CONCLUSIONS
  PFS at 6 and 9 months predicted OS in this analysis of patients with metastatic UC treated with first-line cisplatin-based chemotherapy and could potentially serve as endpoints in (randomized) phase 2 trials to screen the activity of novel regimens.
authors.affiliation: Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY 10029, USA. matthew.galsky@mssm.edu
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
authors.forename: Susan
authors.initials: S
authors.lastname: Krege
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lin
authors.forename: Noah
authors.initials: N
authors.lastname: Hahn
authors.forename: Thorsten
authors.initials: T
authors.lastname: Ecke
authors.forename: Erin
authors.initials: E
authors.lastname: Moshier
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: James
authors.initials: J
authors.lastname: Godbold
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
authors.forename: Aristotle
authors.initials: A
authors.lastname: Bamias
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D002945:Cisplatin
keywords: bladder cancer; chemotherapy; cisplatin; clinical trials; overall survival; progression-free survival; urothelial cancer