| Phase II results for ZD6474 alone
or in combination against advanced non-small cell lung cancer are released as
enrollment begins for international phase III study The targeted agent ZD6474 shows promise in combination and as a single agent against advanced non-small cell lung cancer that has failed platinum-based chemotherapy, according to a pair of presentations at the annual meeting of the American Society of Clinical Oncology. The results come from two phase II studies, both of which were looking for optimal use of ZD6474, a compound that targets both epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGF) cell signaling pathways. Both studies met their primary endpoint of progression free survival (PFS). "Lung cancer is not a single entity but rather a heterogeneous disease making it difficult to treat," said Roy Herbst, MD., PhD, The University of Texas M. D. Anderson Cancer Center, Houston, and principal investigator of Study 32, a phase III trial that has begun enrolling patients worldwide. "The potential to selectively target multiple key signaling pathways involved in tumor growth with investigational agents may provide an additional benefit to patients suffering from lung cancer." In one trial (Abstract 7016), 127 patients with advanced non-small cell lung cancer who were receiving docetaxel after failure of first-line platinum-based chemotherapy were randomized to 100 or 300 mg ZD6474 or to placebo. Addition of 100 mg ZD6474 increased median progression-free survival to 19 weeks and 300 mg ZD6474 increased the median to 17 weeks compared with 12 weeks with docetaxel plus placebo. The most common side effects seen with ZD6474 were rash, diarrhea and asymptomatic QT prolongation. "In Phase II studies, ZACTIMA has shown anti-tumor activity when used in combination with standard chemotherapy and when used as a single agent," said lead investigator John Heymach, MD, PhD, The University of Texas M. D. Anderson Cancer Center, Houston. "Given the poor prognosis in lung cancer, any increase in progression free survival can be meaningful for patients. The preliminary results from Trial 006 have led to the initiation of the Phase III evaluation of ZACTIMA." A two-part study (Abstract 7000) compared anti-tumor effects of 300 mg ZD6474 administered as monotherapy to effects for 250 mg gefitinib administered as monotherapy in 168 patients with advanced non-small-cell lung cancer who had failed first and/or second-line platinum-based chemotherapy. In Part A, patients receiving ZD6474 300 mg had a statistically significant prolongation of progression-free survival compared with gefitinib 250 mg (mean of 11.9 weeks versus 8.1 weeks). Furthermore, disease control for more than 8 weeks was achieved in 45 percent (37/83) of patients receiving ZD6474 compared with 34 percent (29/85) of those receiving gefitinib. In Part B, in which eligible patients had the option to switch to the alternative treatment, disease control for more than 8 weeks was achieved in 43 percent (16/37) of patients who switched to ZD6474 and in 24 percent (7/29) of those who switched to gefitinib. The most common side effects seen in this study were similar to those seen in the other trial, including rash, diarrhea and asymptomatic QT prolongation. In both studies, possibly due to the small number of patients involved and the fact that survival data was potentially confounded by subsequent therapies, there was no significant effect of ZD6474 on overall survival. Both progression free survival and survival outcomes will be investigated in Phase III trials. |