Mature results from Hoosier Oncology Group GU04-75 phase II trial of cisplatin (C), gemcitabine (G), and bevacizumab (B) as first-line chemotherapy for metastatic urothelial carcinoma (UC).

Abstract

4541 Background: Initial results of CGB therapy in metastatic UC patients demonstrated encouraging response and overall survival results with concerning rates of toxicity (Hahn et al ASCO 2008, abst 5018). This summary provides updated results of CGB efficacy and toxicity with mature patient followup. Methods: Metastatic or unresectable chemonaive UC patients (pts) received C 70 mg/m2 iv d1, G 1000- 1250 mg/m2 iv d1, 8, and B 15 mg/kg iv d1 on a q21d cycle as previously described. The primary endpoint was progression-free survival (PFS). Results: 43pts were enrolled and treated. Patient demographics have previously been described. Grade 3-4 hematologic toxicity included: neutropenia 35%, thrombocytopenia 12%, anemia 12%, and neutropenic fever 2%. Grade 3-4 non-hematologic toxicity included: DVT/PE 21%, hemorrhage 7%, hypertension 5%, and proteinuria 2%. 3 treatment related deaths (1 CNS hemorrhage, 1 sudden cardiac death, 1 aortic dissection) were observed. Only 2 DVT/PE events were observed following protocol amended G dose reduction. Best RECIST response was: complete response 9 pts (21%, 95% CI 10-36%), partial response 22 pts (51%, 95% CI 36-67%); with overall response rate of 72% (95% CI 56-85%). Stable disease lasting at least 12 weeks was observed in 7 pts (16%, 95% CI 7-31%) and progressive disease in 4 pts (10%, 95% CI 3- 22%). With a median followup of 27.2 months (Range 1.6-40.9), median PFS was 8.2 months (95% CI 7.3 – 10.5) with a median overall survival (OS) of 20.4 months (95% CI 14.7 – 23.4). Unplanned multivariable analysis revealed significant associations between improved OS and less than two metastatic sites (p<0.01), female gender (p<0.01), G dose 1250 mg/m2 (p=0.03), and lower body mass index (BMI) (p=0.02). Significant univariate associations between higher toxicity rates and higher BMI (p=0.01), and G dose 1250 mg/m2 (p< 0.01) were also observed. Conclusions: CGB is an active first-line regimen in metastatic UC. Known anti-angiogenic treatment related toxicites (bleeding, thromboembolism) are common. The risk/benefit profile of CGB in metastatic UC patients is under further study in a phase III intergroup trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Genentech Lilly Genentech Genentech