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

Cancer. 2009 Jul 1;115(13):2881-90. doi: 10.1002/cncr.24337.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Carcinoma, Transitional Cell / drug therapy*
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / secondary
  • Disease Progression
  • Female
  • Humans
  • Lapatinib
  • Male
  • Middle Aged
  • Platinum Compounds / therapeutic use
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Survival Analysis
  • Time Factors
  • Treatment Outcome
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / secondary

Substances

  • Platinum Compounds
  • Quinazolines
  • Lapatinib