alexa 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.
Molecular Biology

Molecular Biology

Journal of Cytology & Histology

Author(s): Wlfing C, Machiels JP, Richel DJ, Grimm MO, Treiber U,

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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. This article was published in Cancer and referenced in Journal of Cytology & Histology

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