The ZODIAC, (Zactima in cOmbination with Docetaxel In non-smAll cell lung Cancer) study enrolled 1,391 patients with non-small cell lung cancer from 198 centers between May 2006 and April 2008; all had received chemotherapy previously. Participants were randomized to receive either docetaxel and placebo, or docetaxel and vandetanib. The median follow-up was 12.8 months and the study's primary endpoint was progression-free survival.
Patients in the combination arm had a 21 percent reduction in disease progression, compared to those who received docetaxel alone (hazard ratio, .79), and their median progression-free survival was 17.3 weeks. In contrast, the median progression-free survival in the control arm was 14 weeks. While it trended positive, however, there was no statistical difference in overall survival in the two groups. There was a statistically significant improvement in the time to worsening of symptoms (hazard ratio, .77).
"Obviously, our ultimate goal is to always improve survival for our patients, however the improved time to progression with less of a number of significant effects is important," said Herbst. "This is certainly a drug, where, if we could identify molecular parameters that predict response, we could some day take a group that's receiving docetaxel and vandetanib and see them do even better. We're not there yet, but hopefully this study will serve as the foundation for the merger of personalization and discovery with the now-proven safety and efficacy."
In terms of side effects, patients who received vandetanib experienced more diarrhea, rash and neutropenia. However, they experienced less of the significant side effects - nausea, vomiting, and anemia - than those who received docetaxel alone. The lack of significant side effects is quite striking, said Herbst, because other agents that target VEGF are associated with increased toxicity, including pulmonary bleeding.
|Contact: Laura Sussman|
University of Texas M. D. Anderson Cancer Center