TY - JOUR
T1 - Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer
AU - Heymach, John V.
AU - Paz-Ares, Luis
AU - De Braud, Filippo
AU - Sebastian, Martin
AU - Stewart, David J.
AU - Eberhardt, Wilfried E.E.
AU - Ranade, Anantbhushan A.
AU - Cohen, Graham
AU - Trigo, Jose Manuel
AU - Sandler, Alan B.
AU - Bonomi, Philip D.
AU - Herbst, Roy S.
AU - Krebs, Annetta D.
AU - Vasselli, James
AU - Johnson, Bruce E.
N1 - Funding Information:
Received 1 October 1998; accepted 12 October 1999. The support of the Land and Water Resources Research and Development Corporation, through project UME29, is gratefully acknowledged. Address correspondence to Sarah Ewing, Centre for Environmental Applied Hydrology, Department of Civil and Environmental Engineering, University of Melbourne, Parkville, Victoria 3010, Australia. E-mail : s.ewing@ civag.unimelb.edu.au
PY - 2008/11/20
Y1 - 2008/11/20
N2 - Purpose: Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non-small-cell lung cancer (NSCLC). Patients and Methods: All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study. Patients were randomly assigned 2:1:1 to receive vandetanib, VPC, or PC. Progression-free survival (PFS) was the primary end point, and the study was powered to detect a reduced risk of progression with VPC versus PC (hazard ratio = 0.70; one-sided P < .2) and to demonstrate noninferiority for vandetanib versus PC. Overall survival was a secondary assessment. Results: The risk of progression was reduced for patients receiving VPC (n = 56) versus PC (n = 52; hazard ratio = 0.76, one-sided P = .098); median PFS was 24 weeks (VPC) and 23 weeks (PC). The vandetanib monotherapy arm (n = 73) was discontinued after a planned interim PFS analysis met the criterion for discontinuation (hazard ratio > 1.33 v PC). Overall survival was not significantly different between patients receiving VPC or PC. Rash, diarrhea, and hypertension were common adverse events; no pulmonary or CNS hemorrhage events required intervention. Conclusion: VPC could be safely administered to patients with NSCLC, including those with squamous cell histology and treated brain metastases. Compared with the PC control arm, patients receiving VPC had longer PFS, meeting the prespecified study end point, whereas those receiving vandetanib monotherapy had shorter PFS.
AB - Purpose: Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non-small-cell lung cancer (NSCLC). Patients and Methods: All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study. Patients were randomly assigned 2:1:1 to receive vandetanib, VPC, or PC. Progression-free survival (PFS) was the primary end point, and the study was powered to detect a reduced risk of progression with VPC versus PC (hazard ratio = 0.70; one-sided P < .2) and to demonstrate noninferiority for vandetanib versus PC. Overall survival was a secondary assessment. Results: The risk of progression was reduced for patients receiving VPC (n = 56) versus PC (n = 52; hazard ratio = 0.76, one-sided P = .098); median PFS was 24 weeks (VPC) and 23 weeks (PC). The vandetanib monotherapy arm (n = 73) was discontinued after a planned interim PFS analysis met the criterion for discontinuation (hazard ratio > 1.33 v PC). Overall survival was not significantly different between patients receiving VPC or PC. Rash, diarrhea, and hypertension were common adverse events; no pulmonary or CNS hemorrhage events required intervention. Conclusion: VPC could be safely administered to patients with NSCLC, including those with squamous cell histology and treated brain metastases. Compared with the PC control arm, patients receiving VPC had longer PFS, meeting the prespecified study end point, whereas those receiving vandetanib monotherapy had shorter PFS.
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U2 - 10.1200/JCO.2008.17.3138
DO - 10.1200/JCO.2008.17.3138
M3 - Article
C2 - 18936474
AN - SCOPUS:56749102822
SN - 0732-183X
VL - 26
SP - 5407
EP - 5415
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 33
ER -