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

• Published in: Cancer Vol. 115; no. 13; pp. 2881 - 2890
• Main Authors: Wülfing, Christian, Machiels, Jean‐Pascal H., Richel, Dirk J., Grimm, Marc‐Oliver, Treiber, Uwe, De Groot, Marco R., Beuzeboc, Philippe, Parikh, Roma, Pétavy, Frank, El‐Hariry, Iman A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2009; Wiley-Blackwell
• Subjects: Administration, Oral; Adult; Aged; Biological and medical sciences; bladder cancer; Carcinoma, Transitional Cell - drug therapy; Carcinoma, Transitional Cell - pathology; Carcinoma, Transitional Cell - secondary; Disease Progression; dual tyrosine kinase inhibitor; epidermal growth factor receptor; Female; HER‐2; Humans; lapatinib; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Platinum Compounds - therapeutic use; Quinazolines - administration & dosage; Quinazolines - adverse effects; Quinazolines - therapeutic use; Survival Analysis; Time Factors; transitional cell carcinoma; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - secondary; Urinary tract. Prostate gland; Antineoplastic agent; Multicenter study; erbB2 Gene; Transitional cell carcinoma; Metastasis; HER-2; Epidermal growth factor receptor; Cancerology; Phase II trial; dual tyrosine kinase inhibitor; Advanced stage; Second line treatment; Lapatinib; Protein-tyrosine kinase; Protooncogene; Human; Urinary system disease; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Urinary tract disease; Malignant tumor; Bladder cancer; Human Epidermal growth factor Receptor 2; Growth factor receptor; C-Onc gene; Bladder disease; Locally advanced stage; Arm; Cancer
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.24337

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. The purpose of this study was to investigate 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 transitional cell carcinoma, an area that remains of high unmet clinical need. Although the study was negative, failing to meet its primary endpoint of objective response rate, an improvement in overall survival was demonstrated in a subset of patients with EGFR and/or HER‐2 overexpression, which is encouraging and warrants further investigation.