title: A single-arm, multicenter, open-label phase 2 study of lapatinib as the second-line treatment of patients with locally advanced or metastatic transitional cell carcinoma.
abstract: BACKGROUND
  The treatment of recurrent transitional cell carcinoma (TCC) remains an unmet clinical need. This study assessed lapatinib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and HER-2, as second-line therapy in patients with locally advanced or metastatic TCC.
  
  
  METHODS
  This was a single-arm, multicenter, open-label, prospective phase 2 study. Patients with TCC whose disease progressed on prior platinum-based chemotherapy received lapatinib until disease progression or unacceptable toxicity, with evaluations for response by Response Evaluation Criteria In Solid Tumors criteria performed every 8 weeks. The primary endpoint of the current study was objective tumor response rate. Secondary endpoints included safety, time to disease progression, and overall survival.
  
  
  RESULTS
  Fifty-nine patients were enrolled in the study, 25 of whom (42%) could not be evaluated for response. The primary endpoint of an objective response rate (ORR) >10% was observed in 1.7% (95% confidence interval [95% CI], 0.0%-9.1%) of patients; however, 18 (31%; 95% CI, 19%-44%) patients achieved stable disease (SD). The median time to disease progression and overall survival (OS) were 8.6 weeks (95% CI, 8.0 weeks-11.3 weeks) and 17.9 weeks (95% CI, 13.1 weeks-30.3 weeks), respectively. Clinical benefit (ORR and SD) was found to be correlated with EGFR overexpression (P = .029), and, to some extent, HER-2 overexpression. The median OS was significantly prolonged in patients with tumors that overexpressed EGFR and/or HER-2 (P = .0001). Lapatinib was well tolerated.
  
  
  CONCLUSIONS
  The study was considered to be negative because it did not meet its primary endpoint; however, further analysis demonstrated an improvement in OS in a subset of patients with tumors overexpressing EGFR and/or HER-2, which is encouraging and warrants further investigation.
authors.affiliation: Department of Urology, University of Münster, Münster, Germany. wulfing@uni-muenster.de
authors.forename: Christian
authors.initials: C
authors.lastname: Wülfing
authors.forename: Jean-Pascal H
authors.initials: JP
authors.lastname: Machiels
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Richel
authors.forename: Marc-Oliver
authors.initials: MO
authors.lastname: Grimm
authors.forename: Uwe
authors.initials: U
authors.lastname: Treiber
authors.forename: Marco R
authors.initials: MR
authors.lastname: De Groot
authors.forename: Philippe
authors.initials: P
authors.lastname: Beuzeboc
authors.forename: Roma
authors.initials: R
authors.lastname: Parikh
authors.forename: Frank
authors.initials: F
authors.lastname: Pétavy
authors.forename: Iman A
authors.initials: IA
authors.lastname: El-Hariry
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary
chemical_list: D017671:Platinum Compounds; D011799:Quinazolines; D000077341:Lapatinib