Source: DGNews  |  Posted 2 years ago

By Deborah Brauser

ORLANDO, Fla -- June 2, 2009 -- Adding vandetanib to docetaxel increases progression-free survival compared with docetaxel monotherapy for patients with advanced non-small-cell lung cancer (NSCLC) whose disease has progressed after first-line treatment, according to researchers presenting here at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO).

"Vandetanib is the first oral targeted therapy in phase 3 trials to show significant evidence of clinical benefit when added to standard chemotherapy in [NSCLC]," stated lead author Roy S. Herbst, MD, PhD, University of Texas M. D. Anderson Cancer Center, Houston, Texas, presenting the results of the Zactima in Combination With Docetaxel in Non-Small Cell Lung Cancer (ZODIAC) trial here on May 31.

Between May 2006 and April 2008, 1,391 patients (mean age 58 years, 70% male, 25% squamous disease, and 10% with brain metastases) were enrolled from 198 centres. The patients, all of whom had received chemotherapy previously, were randomised to receive either vandetanib 100 mg/day plus docetaxel 75 mg/m² every 21 days (maximum 6 cycles; n = 694) or the docetaxel treatment plus placebo (n = 697).

The primary endpoint was prolonged progression-free survival. Secondary endpoints included overall survival, objective response rate, time to deterioration of symptoms, and safety. The median follow-up was 12.8 months.

Results showed a 21% reduction in disease progression for the vandetanib plus docetaxel group, compared with those in the docetaxel group (hazard ratio [HR], 0.79; 97.58% confidence interval [CI], 0.70 to 0.90; P < .001). In addition, the patients treated with vandetanib plus docetaxel had a median progression-free survival time of 17.3 weeks versus 14 weeks for the docetaxel group.

The vandetanib plus docetaxel group also showed an increase in overall response rate at 17% versus 10% in the docetaxel group (P < .001) and time to deterioration of symptoms (HR, 0.78; P = .002).

Although it was not statistically significant, there was a positive trend for overall survival in the vandetanib plus docetaxel group (HR, 0.91; 97.52% CI, 0.78 to 1.07; P = .196).

Several common adverse events occurred more frequently in the vandetanib plus docetaxel group than in the docetaxel group, including diarrhoea (42% vs 33%), rash (42% vs 24%), and neutropenia (32% vs 27%). "About 22% of the study patients discontinued vandetanib due to side effects," reported Dr. Herbst. "But this [discontinuation rate] is relatively low for a second-line therapy in advanced lung cancer."

Side effects that occurred less frequently in the vandetanib plus docetaxel group than in the docetaxel group included nausea (23% vs 32%), vomiting (16% vs 21%), and anaemia (10% vs 15%).

"This study shows that an oral tyrosine kinase inhibitor can be combined with chemotherapy safely and effectively to provide significant benefits," said Dr. Herbst. "And it worked in both squamous and nonsquamous patients."

"While the study will have immediate clinical implications, we still need to build on the research and turn our focus toward better identifying molecular markers involved, with the ultimate goal of personalising our patients' care," Dr. Herbst concluded.

He added that he plans to update the survival data later this year.

[Presentation title: Vandetanib Plus Docetaxel Versus Docetaxel as Second-Line Treatment for Patients With Advanced Non-Small Cell Lung Cancer (NSCLC): A Randomized, Double-Blind Phase III Trial (ZODIAC). Abstract CRA8003]