Vandetanib given in addition to a standard chemotherapy regimen of docetaxel prolongs progression-free survival (PFS) and improves response rates compared with standard chemotherapy alone in patients with previously treated advanced non-small-cell lung cancer (NSCLC). These findings are the first to show significant evidence of an additional benefit when an oral targeted agent is combined with standard chemotherapy for lung cancer, according to an Article published Online First in The Lancet Oncology.
NSCLC accounts for about 85% of lung cancer cases, and is the leading cause of cancer death worldwide. The drug vandetanib is designed to target two receptors that play a key role in the growth and spread of NSCLC—epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR). A previous phase 2 trial has shown that vandetanib has promising antitumour activity and increases PFS in previously treated patients with advanced NSCLC.
To further evaluate the potential of vandetanib as a treatment for advanced NSCLC, Roy S Herbst from the University of Texas MD Anderson Cancer Center, USA, and international colleagues established the phase 3 ZODIAC trial. 1391 patients who had previously received chemotherapy were recruited from 25 countries between May, 2006, and April, 2008. Patients were randomly assigned to vandetanib plus docetaxel (694) or placebo plus docetaxel (697) and followed up for an average of 12.8 months.
Overall, patients in the vandetanib group had significantly longer PFS (4.0 months) compared to the placebo group (3.2 months). While there was no significant difference in overall survival between the groups, the objective response rate* was significantly higher in the vandetanib group (17% vs 10%). Additionally, vandetanib treatment was associated with a significant improvement in time to worsening of symptoms (3.5 months vs 2.7 months).
The safety profile seen in this study is similar to that shown in other vandetanib studies. The most common side-effects found in patients in the combination group compared to placebo were diarrhoea (42% vs 33%), rash (42% vs 24%), and neutropenia (32% vs 27%). Interestingly, patients receiving vandetanib experienced a lower rate of nausea (23% vs 32%), vomiting (16% vs 21%), and anaemia (10% vs 15%).
The authors comment: "Adding vandetanib to docetaxel in patients with previously treated advanced NSCLC can slow disease progression and this is associated with better control of the symptoms caused by lung cancer…[and] raises the possibility that patients with this advanced disease can live with fewer symptoms (and consequently fewer interventions) for a longer period of time…leading to an important palliative benefit."
Professor Roy S Herbst, University of Texas MD Anderson Cancer Center, Houston, USA. T) +1 713 705 6689 (mobile) E) rherbst@mdanderson.org
Journal
The Lancet Oncology