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
Author(s) -
Wülfing Christian,
Machiels JeanPascal H.,
Richel Dirk J.,
Grimm MarcOliver,
Treiber Uwe,
De Groot Marco R.,
Beuzeboc Philippe,
Parikh Roma,
Pétavy Frank,
ElHariry Iman A.
Publication year - 2009
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24337
Subject(s) - medicine , lapatinib , oncology , phases of clinical research , open label , second line , multicenter study , first line , cancer , chemotherapy , clinical trial , trastuzumab , breast cancer , randomized controlled trial
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. Cancer 2009. © 2009 American Cancer Society.