BEAM: a randomized phase II study evaluating the activity of bevacizumab in
combination with carboplatin plus paclitaxel in patients with previously
untreated advanced melanoma.
Author(s): Kim KB, Sosman JA, Fruehauf JP, Linette GP, Markovic SN, McDermott DF, Weber JS,
Nguyen H, Cheverton P, Chen D, Peterson AC, Carson WE 3rd, O'Day SJ.
Affiliation(s): The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Publication date & source: 2012, J Clin Oncol. , 30(1):34-41
PURPOSE: Metastatic melanoma, a highly vascularized tumor with strong expression
of vascular endothelial growth factor, has an overall poor prognosis. We
conducted a placebo-controlled, double-blind phase II study of carboplatin plus
paclitaxel with or without bevacizumab in patients with previously untreated
metastatic melanoma.
PATIENTS AND METHODS: Patients were randomly assigned in a two-to-one ratio to
carboplatin (area under the curve, 5) plus paclitaxel (175 mg/m(2)) and
bevacizumab (15 mg/kg; CPB) or placebo (CP) administered intravenously once every
3 weeks. Progression-free survival (PFS) was the primary end point. Secondary end
points included overall survival (OS) and safety.
RESULTS: Two hundred fourteen patients (73% with M1c disease) were randomly
assigned. With a median follow-up of 13 months, median PFS was 4.2 months for the
CP arm (n = 71) and 5.6 months for the CPB arm (n = 143; hazard ratio [HR], 0.78;
P = .1414). Overall response rates were 16.4% and 25.5%, respectively (P =
.1577). With 13-month follow-up, median OS was 8.6 months in the CP arm versus
12.3 months in the CPB arm (HR, 0.67; P = .0366), whereas in an evaluation 4
months later, it was 9.2 versus 12.3 months, respectively (HR, 0.79; P = .1916).
In patients with elevated serum lactate dehydrogenase (n = 84), median PFS and OS
were longer in the CPB arm (PFS: 4.4 v 2.7 months; HR, 0.62; OS: 8.5 v 7.5
months; HR, 0.52). No new safety signals were observed.
CONCLUSION: The study did not meet the primary objective of statistically
significant improvement in PFS with the addition of bevacizumab to carboplatin
plus paclitaxel. A larger phase III study will be necessary to determine whether
there is benefit to the addition of bevacizumab to carboplatin plus paclitaxel in
this disease setting.
|
