BEAM

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

Kevin B. Kim, Jeffrey A. Sosman, John P. Fruehauf, Gerald P. Linette, Svetomir Nenad Markovic, David F. McDermott, Jeffrey S. Weber, Hoa Nguyen, Peter Cheverton, Daniel Chen, Amy C. Peterson, William E. Carson, Steven J. O'Day

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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.

Original languageEnglish (US)
Pages (from-to)34-41
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number1
DOIs
StatePublished - Jan 1 2012

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Carboplatin
Paclitaxel
Disease-Free Survival
Melanoma
Survival
Placebos
Safety
L-Lactate Dehydrogenase
Vascular Endothelial Growth Factor A
Area Under Curve
Bevacizumab
Serum
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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BEAM : A randomized phase II study evaluating the activity of bevacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated advanced melanoma. / Kim, Kevin B.; Sosman, Jeffrey A.; Fruehauf, John P.; Linette, Gerald P.; Markovic, Svetomir Nenad; McDermott, David F.; Weber, Jeffrey S.; Nguyen, Hoa; Cheverton, Peter; Chen, Daniel; Peterson, Amy C.; Carson, William E.; O'Day, Steven J.

In: Journal of Clinical Oncology, Vol. 30, No. 1, 01.01.2012, p. 34-41.

Research output: Contribution to journalArticle

Kim, KB, Sosman, JA, Fruehauf, JP, Linette, GP, Markovic, SN, McDermott, DF, Weber, JS, Nguyen, H, Cheverton, P, Chen, D, Peterson, AC, Carson, WE & O'Day, SJ 2012, 'BEAM: A randomized phase II study evaluating the activity of bevacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated advanced melanoma', Journal of Clinical Oncology, vol. 30, no. 1, pp. 34-41. https://doi.org/10.1200/JCO.2011.34.6270
Kim, Kevin B. ; Sosman, Jeffrey A. ; Fruehauf, John P. ; Linette, Gerald P. ; Markovic, Svetomir Nenad ; McDermott, David F. ; Weber, Jeffrey S. ; Nguyen, Hoa ; Cheverton, Peter ; Chen, Daniel ; Peterson, Amy C. ; Carson, William E. ; O'Day, Steven J. / BEAM : A randomized phase II study evaluating the activity of bevacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated advanced melanoma. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 1. pp. 34-41.
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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.",
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T2 - A randomized phase II study evaluating the activity of bevacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated advanced melanoma

AU - Kim, Kevin B.

AU - Sosman, Jeffrey A.

AU - Fruehauf, John P.

AU - Linette, Gerald P.

AU - Markovic, Svetomir Nenad

AU - McDermott, David F.

AU - Weber, Jeffrey S.

AU - Nguyen, Hoa

AU - Cheverton, Peter

AU - Chen, Daniel

AU - Peterson, Amy C.

AU - Carson, William E.

AU - O'Day, Steven J.

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N2 - 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.

AB - 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.

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