BEAM: a randomized phase II study evaluating the activity of bevacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated advanced melanoma

Abstract

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.

Fig 1.

CONSORT diagram. CP, carboplatin plus paclitaxel and placebo; CPB, carboplatin plus paclitaxel and bevacizumab.

Fig 2.

Kaplan-Meier estimated survival for all patients by treatment group: (A) progression-free survival (PFS) and (B) overall survival (OS) as of April 2009. Kaplan-Meier estimated survival for patients with poor prognosis by treatment group: (C) PFS and (D) OS for patients with M1c stage cancer; (E) PFS and (F) OS for patients with M1c stage cancer and elevated serum lactate dehydrogenase levels. CP, carboplatin plus paclitaxel and placebo; CPB, carboplatin plus paclitaxel and bevacizumab; HR, hazard ratio.

Fig 3.

Analysis of median survival by subgroups for all randomly assigned patients. (A) Progression-free survival (PFS); (B) overall survival (OS). CP, carboplatin plus paclitaxel and placebo; CPB, carboplatin plus paclitaxel and bevacizumab; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; NE, not estimable.

Fig 3.

Analysis of median survival by subgroups for all randomly assigned patients. (A) Progression-free survival (PFS); (B) overall survival (OS). CP, carboplatin plus paclitaxel and placebo; CPB, carboplatin plus paclitaxel and bevacizumab; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; NE, not estimable.