Trastuzumab (T), paclitaxel (P), carboplatin (C), and gemcitabine (G) in advanced HER2-positive urothelial carcinoma: Results of a multi-center phase II NCI trial

4507 Background: We have previously reported a > 50% HER2 overexpression in patients (pts) with metastatic urothelial cancer (UC). Methods: Metastatic UC pts were screened for HER2 overexpression. Pts eligible for therapy had: HER2 overexpression by immunohisto-chemistry (IHC) (2+ or 3+) and/or gene amplification by FISH (> 2 by Vysis) and/or elevated serum HER2 >16 ng/ml by OSDI; no prior chemotherapy for metastasis (mets); normal cardiac function, performance status (PS) 0–2; and adequate organ function. HER2 assays were performed centrally. Pts received T 4mg/kg loading dose followed by 2mg/kg on days (D) 1, 8, & 15; P 200 mg/m2 D1; C (AUC 5) on D1; G 800 mg/m2 on D 1& 8. Response and MUGA were assessed Q 3 cycles. Primary end point: toxicity of TPCG. Secondary endpoints: efficacy, survival, time to progression (TTP) and prospective evaluation of HER2 status. Results: 59/109 registered pts (54%) were HER2 positive (+ve) (IHC 51%, FISH 13%, serology 12%). Based on the higher of the IHC score from primar...