Trastuzumab (T) combined with standard chemotherapy in HER+ metastatic bladder cancer (BC) patients: Interim safety results of a prospective randomized phase II study

Abstract

15565 Background: Almost 25% of BC patients overexpressed HER2 and 50 to 60% of them are responding to the combination of T with standard chemotherapy (gemcitabine and platinum salt). A prospective, randomized, European phase II study comparing this association with conventional chemotherapy alone is ongoing. Methods: Eligible HER+ BC pts were required to have an advanced and chemonaive bladder cancer and ECOG performance status (PS) 0–2. The aim is to demonstrate a progression-free survival benefit for investigational arm. Sample size was estimated at 126 patients, with a two-sided alpha and beta levels at 5 and 80%, respectively. Treatment-related toxicities were evaluated using CTC-NCI version 2. Fisher exact test was the main statistical method testing differences in percentage of toxicities. Results: Thirty-seven patients were included in 11 centres between February 2004 and December 2006. The planned safety interim analysis was performed after inclusion of 30 patients (15 in each arm). Median age was 59 years (range 46- 80), 93% of patients are men. Seven percent have an advanced disease, 33% have more than one single metastatic site and 83% were PS ECOG 0–1. There were no significant differences between arms concerning hematological and non-hematological all grade toxicities. Severe (grade III-IV) leucopenia, granulocytopenia, anemia and thrombocytopenia were registered in 53, 53, 33 and 60% for combined arm. Grade I-II of diarrhea was slightly more frequent for T arm. There were no differences for alopecia, constipation, nausea and edema. An asymptomatic reduction of the left ventricular ejection fraction was found in one patient in each arm. Conclusions: Combination of T with standard chemotherapy for BC patients was safe. No serious adverse events significant differences were registered, especially concerning T-related cardiac toxicities. The planned interim efficacy analysis is expected after inclusion of 60 patients. No significant financial relationships to disclose.