Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non-small-cell lung cancer

John V. Heymach, Bruce E. Johnson, Diane Prager, Edit Csada, Jaromǐr Roubec, Miloš Pešek, Irena Špásová, Chandra Belani, István Bodrogi, Shirish Gadgeel, Sarah J. Kennedy, Jeannie Hou, Roy S. Herbst

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Abstract

Purpose: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor kinase activity. The activity of vandetanib plus docetaxel was assessed in patients with previously treated non-small-cell lung cancer (NSCLC). Patients and Methods: This two-part study comprised an open-label run-in phase and a double-blind randomized phase. Eligible patients had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of first-line platinum-based chemotherapy. The primary objective of the randomized phase was to prolong progression-free survival (PFS) in patients receiving vandetanib (100 or 300 mg/d) plus docetaxel (75 mg/m2 intravenous infusion every 21 days) versus placebo plus docetaxel. The study was designed to have more than 75% power to detect 50% prolongation at a one-sided significance level of P < .20. Secondary objectives included objective response rate, overall survival, safety and tolerability. Results: In the randomized phase (n = 127), median PFS was 18.7 weeks for vandetanib 100 mg plus docetaxel (n = 42; hazard ratio v docetaxel = 0.64; one-sided P = .037); 17.0 weeks for vandetanib 300 mg plus docetaxel (n = 44; hazard ratio v docetaxel = 0.83; one-sided P = .231); and 12 weeks for docetaxel (n = 41). There was no statistically significant difference in overall survival among the three treatment arms. Common adverse events included diarrhea, rash, and asymptomatic prolongation of corrected QT (QTC) interval. Conclusion: The primary objective was achieved, with vandetanib 100 mg plus docetaxel demonstrating a significant prolongation of PFS compared with docetaxel in relation to the prespecified significance level. On the basis of these encouraging data, phase III evaluation of vandetanib 100 mg plus docetaxel in second-line NSCLC has been initiated.

Original languageEnglish (US)
Pages (from-to)4270-4277
Number of pages8
JournalJournal of Clinical Oncology
Volume25
Issue number27
DOIs
StatePublished - Sep 20 2007

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docetaxel
Non-Small Cell Lung Carcinoma
Placebos
Disease-Free Survival
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
Vascular Endothelial Growth Factor Receptor-2

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Heymach, J. V., Johnson, B. E., Prager, D., Csada, E., Roubec, J., Pešek, M., ... Herbst, R. S. (2007). Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non-small-cell lung cancer. Journal of Clinical Oncology, 25(27), 4270-4277. https://doi.org/10.1200/JCO.2006.10.5122
Heymach, John V. ; Johnson, Bruce E. ; Prager, Diane ; Csada, Edit ; Roubec, Jaromǐr ; Pešek, Miloš ; Špásová, Irena ; Belani, Chandra ; Bodrogi, István ; Gadgeel, Shirish ; Kennedy, Sarah J. ; Hou, Jeannie ; Herbst, Roy S. / Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non-small-cell lung cancer. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 27. pp. 4270-4277.
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abstract = "Purpose: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor kinase activity. The activity of vandetanib plus docetaxel was assessed in patients with previously treated non-small-cell lung cancer (NSCLC). Patients and Methods: This two-part study comprised an open-label run-in phase and a double-blind randomized phase. Eligible patients had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of first-line platinum-based chemotherapy. The primary objective of the randomized phase was to prolong progression-free survival (PFS) in patients receiving vandetanib (100 or 300 mg/d) plus docetaxel (75 mg/m2 intravenous infusion every 21 days) versus placebo plus docetaxel. The study was designed to have more than 75{\%} power to detect 50{\%} prolongation at a one-sided significance level of P < .20. Secondary objectives included objective response rate, overall survival, safety and tolerability. Results: In the randomized phase (n = 127), median PFS was 18.7 weeks for vandetanib 100 mg plus docetaxel (n = 42; hazard ratio v docetaxel = 0.64; one-sided P = .037); 17.0 weeks for vandetanib 300 mg plus docetaxel (n = 44; hazard ratio v docetaxel = 0.83; one-sided P = .231); and 12 weeks for docetaxel (n = 41). There was no statistically significant difference in overall survival among the three treatment arms. Common adverse events included diarrhea, rash, and asymptomatic prolongation of corrected QT (QTC) interval. Conclusion: The primary objective was achieved, with vandetanib 100 mg plus docetaxel demonstrating a significant prolongation of PFS compared with docetaxel in relation to the prespecified significance level. On the basis of these encouraging data, phase III evaluation of vandetanib 100 mg plus docetaxel in second-line NSCLC has been initiated.",
author = "Heymach, {John V.} and Johnson, {Bruce E.} and Diane Prager and Edit Csada and Jaromǐr Roubec and Miloš Pešek and Irena Šp{\'a}sov{\'a} and Chandra Belani and Istv{\'a}n Bodrogi and Shirish Gadgeel and Kennedy, {Sarah J.} and Jeannie Hou and Herbst, {Roy S.}",
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Heymach, JV, Johnson, BE, Prager, D, Csada, E, Roubec, J, Pešek, M, Špásová, I, Belani, C, Bodrogi, I, Gadgeel, S, Kennedy, SJ, Hou, J & Herbst, RS 2007, 'Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non-small-cell lung cancer', Journal of Clinical Oncology, vol. 25, no. 27, pp. 4270-4277. https://doi.org/10.1200/JCO.2006.10.5122

Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non-small-cell lung cancer. / Heymach, John V.; Johnson, Bruce E.; Prager, Diane; Csada, Edit; Roubec, Jaromǐr; Pešek, Miloš; Špásová, Irena; Belani, Chandra; Bodrogi, István; Gadgeel, Shirish; Kennedy, Sarah J.; Hou, Jeannie; Herbst, Roy S.

In: Journal of Clinical Oncology, Vol. 25, No. 27, 20.09.2007, p. 4270-4277.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non-small-cell lung cancer

AU - Heymach, John V.

AU - Johnson, Bruce E.

AU - Prager, Diane

AU - Csada, Edit

AU - Roubec, Jaromǐr

AU - Pešek, Miloš

AU - Špásová, Irena

AU - Belani, Chandra

AU - Bodrogi, István

AU - Gadgeel, Shirish

AU - Kennedy, Sarah J.

AU - Hou, Jeannie

AU - Herbst, Roy S.

PY - 2007/9/20

Y1 - 2007/9/20

N2 - Purpose: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor kinase activity. The activity of vandetanib plus docetaxel was assessed in patients with previously treated non-small-cell lung cancer (NSCLC). Patients and Methods: This two-part study comprised an open-label run-in phase and a double-blind randomized phase. Eligible patients had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of first-line platinum-based chemotherapy. The primary objective of the randomized phase was to prolong progression-free survival (PFS) in patients receiving vandetanib (100 or 300 mg/d) plus docetaxel (75 mg/m2 intravenous infusion every 21 days) versus placebo plus docetaxel. The study was designed to have more than 75% power to detect 50% prolongation at a one-sided significance level of P < .20. Secondary objectives included objective response rate, overall survival, safety and tolerability. Results: In the randomized phase (n = 127), median PFS was 18.7 weeks for vandetanib 100 mg plus docetaxel (n = 42; hazard ratio v docetaxel = 0.64; one-sided P = .037); 17.0 weeks for vandetanib 300 mg plus docetaxel (n = 44; hazard ratio v docetaxel = 0.83; one-sided P = .231); and 12 weeks for docetaxel (n = 41). There was no statistically significant difference in overall survival among the three treatment arms. Common adverse events included diarrhea, rash, and asymptomatic prolongation of corrected QT (QTC) interval. Conclusion: The primary objective was achieved, with vandetanib 100 mg plus docetaxel demonstrating a significant prolongation of PFS compared with docetaxel in relation to the prespecified significance level. On the basis of these encouraging data, phase III evaluation of vandetanib 100 mg plus docetaxel in second-line NSCLC has been initiated.

AB - Purpose: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor kinase activity. The activity of vandetanib plus docetaxel was assessed in patients with previously treated non-small-cell lung cancer (NSCLC). Patients and Methods: This two-part study comprised an open-label run-in phase and a double-blind randomized phase. Eligible patients had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of first-line platinum-based chemotherapy. The primary objective of the randomized phase was to prolong progression-free survival (PFS) in patients receiving vandetanib (100 or 300 mg/d) plus docetaxel (75 mg/m2 intravenous infusion every 21 days) versus placebo plus docetaxel. The study was designed to have more than 75% power to detect 50% prolongation at a one-sided significance level of P < .20. Secondary objectives included objective response rate, overall survival, safety and tolerability. Results: In the randomized phase (n = 127), median PFS was 18.7 weeks for vandetanib 100 mg plus docetaxel (n = 42; hazard ratio v docetaxel = 0.64; one-sided P = .037); 17.0 weeks for vandetanib 300 mg plus docetaxel (n = 44; hazard ratio v docetaxel = 0.83; one-sided P = .231); and 12 weeks for docetaxel (n = 41). There was no statistically significant difference in overall survival among the three treatment arms. Common adverse events included diarrhea, rash, and asymptomatic prolongation of corrected QT (QTC) interval. Conclusion: The primary objective was achieved, with vandetanib 100 mg plus docetaxel demonstrating a significant prolongation of PFS compared with docetaxel in relation to the prespecified significance level. On the basis of these encouraging data, phase III evaluation of vandetanib 100 mg plus docetaxel in second-line NSCLC has been initiated.

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