A single arm, multicenter, open label, phase II study of lapatinib as 2L treatment of pts with locally advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract.

4594 Background: Lapatinib is an oral reversible inhibitor of ErbB1 (EGFR) and ErbB2 (HER-2/neu) receptor tyrosine kinases.,The primary endpoint was RECIST response rate. Key eligibility criteria included stage IIIB/IV TCC of the bladder, progression following a first-line platinum regimen, expression of ErbB1 and or ErbB2 (1, 2 or 3+ by IHC) and KPS ≥ 70. Lapatinib (1250 mg, qd) was administered until disease progression or unacceptable toxicity. Tumor and safety assessments were performed every 8 and 4 wks, respectively. Cardiac function was monitored at baseline and every 8 wks. Tumor tissue was analyzed for biomarkers (TUNEL, p53, pAkt, Her3, pHer3, pErk, IGF-1R, Rb, pS6).,Fifty-nine pts were enrolled. Investigators reported 2 (3%) PRs and 12 (20%) SD; independent radiologic review (IRR) reported 1 (2%) PR and 18 (31%) SD. Based upon investigator and IRR, six and three pts had durable SD lasting 4 and 6 mos, respectively. At wk 8, 10 pts had some degree of cytoreduction; however, most was short-lived. One pt remains on study for > 56 wks. The median TTP was 8.6 wks (95% CI, 8.00, 11.29) and median OS was 17.9 wks (95% CI, 13.14, 30.29). A trend towards clinical benefit was observed in pts with 2+/3+ ErbB1 or ErbB2. Preliminary analysis of biomarkers suggests high pHer3, high pErk and both mutant p53 and high pHer3 predicts resistance, and high pAkt and high IGF-1R predicts sensitivity to lapatinib. Adverse events (AEs) with ≥ 10% frequency were diarrhea (39%), rash (32%), nausea (27%), vomiting (22%), asthenia (12%) and fatigue (10%). Grade 3/4 AEs occurring in more than one pt were vomiting (7%) and diarrhea (3%). One pt had an asymptomatic, Grade 2 decrease in LVEF.,Lapatinib was well-tolerated and exhibits activity in pts with relapsed, advanced/metastatic TCC of the bladder, demonstrated by clinical benefit (CR + PR + SD≥ 16 wks) in 14% and 12% of pts by investigator and IRR, respectively. The median TTP of 8.6 wks is comparable to reports of various 2L chemotherapies. There was a trend toward clinical benefit in pts with ErbB1 or ErbB2 2+/3+ by IHC. Multivariate analysis of the biomarker data is planned. [Table: see text].