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

A B S T R A C T PurposeMetastatic 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 MethodsPatients 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. ResultsTwo 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 ϭ 71) and 5.6 months for the CPB arm (n ϭ 143; hazard ratio [HR], 0.78; P ϭ .1414). Overall response rates were 16.4% and 25.5%, respectively (P ϭ .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 ϭ .0366), whereas in an evaluation 4 months later, it was 9.2 versus 12.3 months, respectively (HR, 0.79; P ϭ .1916). In patients with elevated serum lactate dehydrogenase (n ϭ 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. ConclusionThe 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.

A Multicenter Phase I Study of Pazopanib in Combination with Paclitaxel in First-Line Treatment of Patients with Advanced Solid Tumors

“…Because VEGF expression has been shown to play a role in metastatic melanoma (43), studies to explore the combination of carboplatin, paclitaxel, and antiangiogenic agents such as sorafenib and bevacizumab have been performed; however, these studies have not shown improved efficacy compared with the carboplatin and paclitaxel doublet (30,42). In this study, the response rate for melanoma was 29% (5 of 17 patients with PR) with an additional 41% (7 of 17 patients) demonstrating SD of >12 weeks, and one patient diagnosed with ocular melanoma maintained antitumor response for more than 100 weeks.…”

“…Paclitaxel has been used in the first-line treatment of metastatic melanoma both as a single agent and in combination with carboplatin, with reported response rates of approximately 12% to 16% (38)(39)(40) and 16% to 20%, respectively (30,41,42). Because VEGF expression has been shown to play a role in metastatic melanoma (43), studies to explore the combination of carboplatin, paclitaxel, and antiangiogenic agents such as sorafenib and bevacizumab have been performed; however, these studies have not shown improved efficacy compared with the carboplatin and paclitaxel doublet (30,42).…”

Phase I/II Trial of Imatinib and Bevacizumab in Patients With Advanced Melanoma and Other Advanced Cancers

“…We did not enroll patients in the clinical subgroups where these mutations are found. The efficacy of bevacizumab has been explored in combination with carboplatin/paclitaxel in a randomized phase II trial of patients with metastatic melanoma [52]. Marginal and statistically nonsignificant improvements in progression-free survival were observed.…”

Chinese Guidelines on the Diagnosis and Treatment of Melanoma (2015 Edition)

“…Bevacizumab is a monoclonal antibody that can selectively bind VEGF and block its binding with receptors. It has been widely applied in the treatment of metastatic melanoma (182)(183)(184)(185). In a randomized, double-blind phase II study (BEAM study), 214 metastatic melanoma patients were randomized into carboplatin + paclitaxel + bevacizumab (CPB) group or placebo group (CP) at a proportion of 2:1.…”