Phase II Trial of Bevacizumab in Combination With Temozolomide as First-Line Treatment in Patients With Metastatic Uveal Melanoma.

ABSTRACT

BACKGROUND: In experimental models, bevacizumab suppressed in vitro growth and in vivo hepatic metastasis of ocular melanoma cells. Additional preclinical data suggested a potential benefit when combining bevacizumab with dacarbazine. METHODS: This noncomparative phase II study evaluated a combination of bevacizumab (10 mg/kg on days 8 and 22) with temozolomide (150 mg/m(2) on days 1-7 and 15-21) in 36 patients with metastatic uveal melanoma (MUM). The primary endpoint was the progression-free rate (PFR) at 6 months. Using a modified 2-step Fleming plan, at least 10 of 35 patients were required to support a predefined PFR at 6 months of 40%. Secondary objectives were progression-free survival (PFS), overall survival (OS), and safety; liver perfusion computed tomography (CT) for response imaging; and impact of VEGF-A gene polymorphisms on bevacizumab pharmacodynamics. RESULTS: First- and second-step analyses revealed nonprogression at 6 months in 3 of 17 and 8 of 35 patients, respectively. Finally, the 6-month PFR was 23% (95% confidence interval [CI] 10-39), with long-lasting stable disease in 5 patients (14%). Median PFS and OS were 12 weeks and 10 months, respectively. No unexpected toxicity occurred. Liver perfusion CT imaging was not useful in assessing tumor response, and VEGF-A gene polymorphisms were not correlated with toxicity or survival. CONCLUSION: In patients with MUM, a combination of bevacizumab plus temozolomide achieved a 6-month PFR of 23%.