Randomized Phase II Study of Vandetanib Alone or With Paclitaxel and Carboplatin as First-Line Treatment for Advanced Non–Small-Cell Lung Cancer

• Published in: Journal of clinical oncology Vol. 26; no. 33; pp. 5407 - 5415
• Main Authors: Heymach, John V., Paz-Ares, Luis, De Braud, Filippo, Sebastian, Martin, Stewart, David J., Eberhardt, Wilfried E.E., Ranade, Anantbhushan A., Cohen, Graham, Trigo, Jose Manuel, Sandler, Alan B., Bonomi, Philip D., Herbst, Roy S., Krebs, Annetta D., Vasselli, James, Johnson, Bruce E.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.11.2008
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Disease Progression; Female; Humans; Lung Neoplasms - drug therapy; Male; Medical sciences; Middle Aged; Paclitaxel - administration & dosage; Piperidines - administration & dosage; Piperidines - adverse effects; Pneumology; Quinazolines - administration & dosage; Quinazolines - adverse effects; Tumors; Tumors of the respiratory system and mediastinum; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Antineoplastic agent; Lung disease; Vandetanib; Tyrosine kinase inhibitor; Respiratory disease; Lung cancer; Enzyme inhibitor; Malignant tumor; non-small cell lung carcinoma; First line treatment; Randomization; Cancerology; Taxane derivatives; Phase II trial; Paclitaxel; Carboplatin; Bronchus disease; Advanced stage; Multikinase inhibitor; Antiangiogenic agent; Antimitotic; Cancer; Platinum II Complexes
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2008.17.3138

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). 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. 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. 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.