title: Complete response as an intermediate end point in patients receiving salvage systemic therapy for urothelial carcinoma.
abstract: BACKGROUND
  The complete remission (CR) rate with salvage systemic therapy for urothelial carcinoma (UC) is unclear, and its value as an intermediate end point and association with survival are unknown.
  
  
  METHODS
  Data from phase II trials of salvage chemotherapy and/or biologic agents were pooled. Data regarding response, overall survival (OS), progression-free survival (PFS), time from prior chemotherapy, hemoglobin, performance status, and liver metastasis status were collected. Cox proportional hazards regression was used to evaluate the association of CR and other prognostic factors with outcomes.
  
  
  RESULTS
  A total of 789 of 818 patients enrolled in 12 phase II trials had evaluable data. CR and partial response were seen in 14 (1.8%) and 109 (13.8%) patients. Median (95% confidence interval) OS for those with a CR was 21.5 (14.2-34.3) months, compared with 6.7 (6.0-7.0) months in those without a CR (P < .001). Median (95% confidence interval) PFS for those with a CR was 15.7 (8.2-27.1) months, compared with 2.6 (2.4-2.8) months for those without a CR (P < .001). Prior cisplatin and time from prior chemotherapy of ≥ 3 months were associated with CR (P < .05). The presence of poor prognostic factors and suboptimal response to prior therapy did not preclude CR.
  
  
  CONCLUSIONS
  CR occurs in 1.8% of patients receiving salvage therapy for advanced UC and is strongly associated with durable OS and PFS. CR warrants validation as an intermediate end point and may help select agents for further investigation and tumors for molecular interrogation.
authors.affiliation: UAB Comprehensive Cancer Center, Birmingham, AL. Electronic address: gsonpavde@uabmc.edu.
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.affiliation: McMaster University, Ontario, Canada.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Rosenberg
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Bajorin
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Regazzi
authors.affiliation: Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Angela Q
authors.initials: AQ
authors.lastname: Qu
authors.affiliation: Heinrich Heine University, Dusseldorf, Germany.
authors.forename: Guenter
authors.initials: G
authors.lastname: Niegisch
authors.affiliation: Heinrich Heine University, Dusseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Albers
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Necchi
authors.affiliation: University Federico II, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Lorenzo
authors.affiliation: Institut de Recherche Pierre Fabre, Boulogne, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Fougeray
authors.affiliation: Cleveland Clinic, Cleveland, OH.
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
authors.affiliation: Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Yu-Ning
authors.initials: YN
authors.lastname: Wong
authors.affiliation: Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: Srikala S
authors.initials: SS
authors.lastname: Sridhar
authors.affiliation: Sunnybrook Odette Cancer Centre, Toronto, ON, Canada.
authors.forename: Yoo-Joung
authors.initials: YJ
authors.lastname: Ko
authors.affiliation: University of North Carolina, Chapel Hill, NC.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Milowsky
authors.affiliation: Tisch Cancer Center Institute, Mount Sinai School of Medicine, New York, NY.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
authors.affiliation: Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA; University Hospital del Mar-IMIM, Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
mesh_terms: D000368:Aged; D001688:Biological Products / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000187:drug effects / Q000473:pathology*
chemical_list: D001688:Biological Products
keywords: Advanced urothelial carcinoma; Complete response; Overall survival; Partial response; Progression-free survival; Salvage systemic therapy