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.
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: Benjamin A Mooso; Ruth L Vinall; Maria Mudryj; Stanley A Yap; Ralph W deVere White; Paramita M Ghosh Journal: J Urol Date: 2014-08-23 Impact factor: 7.450
Authors: Metin Kurtoglu; Nicole N Davarpanah; Rui Qin; Thomas Powles; Jonathan E Rosenberg; Andrea B Apolo Journal: Clin Genitourin Cancer Date: 2015-03-05 Impact factor: 2.872
Authors: Maha Hussain; Stephanie Daignault; Neeraj Agarwal; Petros D Grivas; Arlene O Siefker-Radtke; Igor Puzanov; Gary R MacVicar; Ellis Glenn Levine; Sandy Srinivas; Przemyslaw Twardowski; Mario A Eisenberger; David I Quinn; Ulka N Vaishampayan; Evan Y Yu; Scott Dawsey; Kathleen C Day; Mark L Day; Mahmoud Al-Hawary; David C Smith Journal: Cancer Date: 2014-05-06 Impact factor: 6.860
Authors: Dmytro M Havaleshko; Steven Christopher Smith; HyungJun Cho; Sooyoung Cheon; Charles R Owens; Jae K Lee; Lance A Liotta; Virginia Espina; Julia D Wulfkuhle; Emanuel F Petricoin; Dan Theodorescu Journal: Neoplasia Date: 2009-11 Impact factor: 5.715