A single arm, multicenter, open-label phase II study of orally administered GW572016 as single-agent, second-line treatment of patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract. Interim analysis

Abstract

4615 Background: GW572016 is an oral, reversible, dual inhibitor of ErbB1 and ErbB2 receptors. This multicenter, phase II trial assessed GW572016 as a single-agent in relapsed urothelial tumors. Objective response rate (RECIST criteria) and toxicity were primary endpoints. Methods: Fifty-eight patients with locally advanced or metastatic urothelial tumors, who had progressed after platinum-based therapy, received 1250 mg GW572016 once daily until disease progression or withdrawal. Safety and efficacy assessments (independent review) were carried out at 4 and 8-week intervals respectively. Patients were also assessed at withdrawal, and followed every 2 months until death. Data from 30 patients were reviewed at an interim analysis (16 weeks on study), and are presented below. Results: The median age was 62 years. Most patients (67%) had visceral metastases. All patients had confirmed expression of ErbB1 and/or ErbB2 (1+, 2+ or 3+ by immunohistochemistry). Only 19 patients (63%) received GW572016 as intended second-line therapy. Three patients (10%) had tumour reduction that was qualified as partial responses (PR) at the initial assessment; however, only one PR was confirmed at 8 weeks. Eight patients (27%) had stable disease (SD), 5 with noted cytoreduction. Clinical benefit (>=6 months SD) was seen in 3 patients (10%). Five patients (17%) had progressive disease, 11 patients (37%) withdrew prior to week 8, and 3 patients (10%) were not evaluable. Disease progression was the most frequent reason for withdrawal. Survival data are not mature at this time. Six patients (20%) experienced serious adverse events of which one, G3 diarrhea, was drug-related as assessed by the investigator. Conclusions: Second-line treatment with oral GW572016 has promising activity and is generally well tolerated in patients with locally advanced or metastatic urothelial tumors. On the basis of these preliminary data, additional trials of GW572016 in urothelial tumors, as mono- or combination therapy, are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline