Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer

Toni K. Choueiri, Robert W. Ross, Susanna Jacobus, Ulka Vaishampayan, Evan Y. Yu, David I. Quinn, Noah M. Hahn, Thomas E. Hutson, Guru Sonpavde, Stephanie C. Morrissey, Geoffrey C. Buckle, William Y. Kim, Daniel P. Petrylak, Christopher Ryan, Mario A. Eisenberger, Amir Mortazavi, Glenn J. Bubley, Mary Ellen Taplin, Jonathan E. Rosenberg, Philip W. Kantoff

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    125 Citations (Scopus)

    Abstract

    Purpose: Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy. Patients and Methods: The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m 2intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60% improvement in median PFS with 80% power and one-sided - at 5%. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives. Results: In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95% CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11% v 0%) and diarrhea (7% v 0%). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3% and OS was 5.2 months. Conclusion: In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal.

    Original languageEnglish (US)
    Pages (from-to)507-512
    Number of pages6
    JournalJournal of Clinical Oncology
    Volume30
    Issue number5
    DOIs
    StatePublished - Feb 10 2012

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    docetaxel
    Platinum
    Placebos
    Disease-Free Survival
    Neoplasms
    Survival
    N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
    Vascular Endothelial Growth Factor Receptor-2

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

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    Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer. / Choueiri, Toni K.; Ross, Robert W.; Jacobus, Susanna; Vaishampayan, Ulka; Yu, Evan Y.; Quinn, David I.; Hahn, Noah M.; Hutson, Thomas E.; Sonpavde, Guru; Morrissey, Stephanie C.; Buckle, Geoffrey C.; Kim, William Y.; Petrylak, Daniel P.; Ryan, Christopher; Eisenberger, Mario A.; Mortazavi, Amir; Bubley, Glenn J.; Taplin, Mary Ellen; Rosenberg, Jonathan E.; Kantoff, Philip W.

    In: Journal of Clinical Oncology, Vol. 30, No. 5, 10.02.2012, p. 507-512.

    Research output: Contribution to journalArticle

    Choueiri, TK, Ross, RW, Jacobus, S, Vaishampayan, U, Yu, EY, Quinn, DI, Hahn, NM, Hutson, TE, Sonpavde, G, Morrissey, SC, Buckle, GC, Kim, WY, Petrylak, DP, Ryan, C, Eisenberger, MA, Mortazavi, A, Bubley, GJ, Taplin, ME, Rosenberg, JE & Kantoff, PW 2012, 'Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer', Journal of Clinical Oncology, vol. 30, no. 5, pp. 507-512. https://doi.org/10.1200/JCO.2011.37.7002
    Choueiri, Toni K. ; Ross, Robert W. ; Jacobus, Susanna ; Vaishampayan, Ulka ; Yu, Evan Y. ; Quinn, David I. ; Hahn, Noah M. ; Hutson, Thomas E. ; Sonpavde, Guru ; Morrissey, Stephanie C. ; Buckle, Geoffrey C. ; Kim, William Y. ; Petrylak, Daniel P. ; Ryan, Christopher ; Eisenberger, Mario A. ; Mortazavi, Amir ; Bubley, Glenn J. ; Taplin, Mary Ellen ; Rosenberg, Jonathan E. ; Kantoff, Philip W. / Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 5. pp. 507-512.
    @article{9be1c81ff18a44cbb102d1e12fd4a453,
    title = "Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer",
    abstract = "Purpose: Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy. Patients and Methods: The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m 2intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60{\%} improvement in median PFS with 80{\%} power and one-sided - at 5{\%}. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives. Results: In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95{\%} CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11{\%} v 0{\%}) and diarrhea (7{\%} v 0{\%}). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3{\%} and OS was 5.2 months. Conclusion: In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal.",
    author = "Choueiri, {Toni K.} and Ross, {Robert W.} and Susanna Jacobus and Ulka Vaishampayan and Yu, {Evan Y.} and Quinn, {David I.} and Hahn, {Noah M.} and Hutson, {Thomas E.} and Guru Sonpavde and Morrissey, {Stephanie C.} and Buckle, {Geoffrey C.} and Kim, {William Y.} and Petrylak, {Daniel P.} and Christopher Ryan and Eisenberger, {Mario A.} and Amir Mortazavi and Bubley, {Glenn J.} and Taplin, {Mary Ellen} and Rosenberg, {Jonathan E.} and Kantoff, {Philip W.}",
    year = "2012",
    month = "2",
    day = "10",
    doi = "10.1200/JCO.2011.37.7002",
    language = "English (US)",
    volume = "30",
    pages = "507--512",
    journal = "Journal of Clinical Oncology",
    issn = "0732-183X",
    publisher = "American Society of Clinical Oncology",
    number = "5",

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    TY - JOUR

    T1 - Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer

    AU - Choueiri, Toni K.

    AU - Ross, Robert W.

    AU - Jacobus, Susanna

    AU - Vaishampayan, Ulka

    AU - Yu, Evan Y.

    AU - Quinn, David I.

    AU - Hahn, Noah M.

    AU - Hutson, Thomas E.

    AU - Sonpavde, Guru

    AU - Morrissey, Stephanie C.

    AU - Buckle, Geoffrey C.

    AU - Kim, William Y.

    AU - Petrylak, Daniel P.

    AU - Ryan, Christopher

    AU - Eisenberger, Mario A.

    AU - Mortazavi, Amir

    AU - Bubley, Glenn J.

    AU - Taplin, Mary Ellen

    AU - Rosenberg, Jonathan E.

    AU - Kantoff, Philip W.

    PY - 2012/2/10

    Y1 - 2012/2/10

    N2 - Purpose: Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy. Patients and Methods: The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m 2intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60% improvement in median PFS with 80% power and one-sided - at 5%. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives. Results: In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95% CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11% v 0%) and diarrhea (7% v 0%). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3% and OS was 5.2 months. Conclusion: In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal.

    AB - Purpose: Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy. Patients and Methods: The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m 2intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60% improvement in median PFS with 80% power and one-sided - at 5%. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives. Results: In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95% CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11% v 0%) and diarrhea (7% v 0%). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3% and OS was 5.2 months. Conclusion: In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal.

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    U2 - 10.1200/JCO.2011.37.7002

    DO - 10.1200/JCO.2011.37.7002

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    VL - 30

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    EP - 512

    JO - Journal of Clinical Oncology

    JF - Journal of Clinical Oncology

    SN - 0732-183X

    IS - 5

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