ATLANTA, June 4 /PRNewswire-FirstCall/ -- AstraZeneca announced today the results of two Phase II studies, Trial 003 and 006, with ZACTIMA (ZD6474), a compound which 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). Presented at the 2006 American Society of Clinical Oncology (ASCO) annual meeting in Atlanta, these new data follow the start of enrollment into the first Phase III study of ZACTIMA in advanced non-small- cell lung cancer, Trial 32, which is expected to enroll more than 1,200 patients worldwide.
"Lung cancer is not a single entity but rather a heterogeneous disease making it difficult to treat," said Roy Herbst, M.D., Ph.D., The University of Texas M. D. Anderson Cancer Center, Houston, and the principal investigator of Study 32. "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."
ZACTIMA (ZD6474) in combination with chemotherapy in advanced NSCLC (Abstract No. 7016)
Trial 006, presented today, evaluated the PFS of ZACTIMA at dosages of 100 mg or 300 mg compared to placebo in 127 patients with advanced non-small-cell lung cancer receiving standard chemotherapy treatment with docetaxel after failure of first-line platinum-based chemotherapy. Results showed that adding ZACTIMA at 100 mg or 300 mg to docetaxel increased median PFS to 19 weeks (HR= 0.64; P=0.074), and 17 weeks (HR=0.83; P=0.461) respectively, compared to 12.0 weeks with docetaxel plus placebo. The most common side effects seen with ZACTIMA (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 Trial 006 lead investigator John Heymach, M.D., 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."
ZACTIMA (ZD6474) as monotherapy in advanced NSCLC (Abstract No. 7000)
In a two-part study, Trial 003 compared the anti-tumor effects of 300 mg of ZACTIMA administered as monotherapy to 250 mg of gefitinib administered as monotherapy in 168 patients with advanced non-small-cell lung cancer after the failure of first and/or second-line platinum-based chemotherapy.
In Part A of the study, patients receiving ZACTIMA 300 mg had a statistically significant prolongation of PFS compared with gefitinib 250 mg, with a mean PFS of 11.9 weeks compared to 8.1 weeks respectively (HR = 0.69; 95% CI 0.50 to0.96, P=0.025). Furthermore, disease control for more than 8 weeks was achieved in 45% (37/83) of patients receiving ZACTIMA compared to 34% (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% (16/37) of patients who switched to ZACTIMA (from gefitinib) and in 24% (7/29) of those who switched to gefitinib (from ZACTIMA). The most common side effects seen in this study were similar to those seen in Trial 6 and included 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 ZACTIMA on overall survival. Both progression free survival and survival outcomes will be investigated in Phase III trials.
ZACTIMA (ZD6474) Phase III study in advanced NSCLC
Study 32, a Phase III study, will evaluate PFS with a combination of ZACTIMA 100 mg plus docetaxel compared to docetaxel alone in patients with advanced NSCLC after failure of a first-line anti-cancer therapy. The study also will assess overall survival, overall disease response and control rates, response duration, effect on disease-related symptoms, quality of life measures, and safety and tolerability as secondary endpoints.
About ZACTIMA (ZD6474)
ZACTIMA is being studied as a multitargeted compound, directed to the inhibition of key cell signaling pathways involved in tumor growth and spread. Tumor cells are targeted through inhibition of epidermal growth factor receptor (EGFR) and REarranged during Transfection (RET) tyrosine kinases, while tumor blood supply is targeted through inhibition of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase. RET tyrosine kinase activity is an important growth driver in certain thyroid tumors.
Additional ZACTIMA (ZD6474) data presented at ASCO (Poster No. 25;Abstract No. 5533)
Further results from Trial 008, an ongoing Phase II study in patients with hereditary medullary thyroid cancer, will be presented at ASCO on June 6, 2006 at 8:00 a.m.
About Lung cancer
Lung cancer is the leading cause of cancer death in the United States in both men and women, according to the American Cancer Society. An estimated 174,470 new cases of lung cancer will be diagnosed in 2006 in the United States, and the disease will account for an estimated 162,460 deaths this year. The 5-year relative survival rate for all stages of lung cancer combined is only 15%.
About AstraZeneca
AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of $23.95 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. In the United States, AstraZeneca is a $10.77 billion healthcare business with more than 12,000 employees. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
For more information about AstraZeneca, please visit: http://www.astrazeneca.com/
This press release contains forward-looking statements with respect to AstraZeneca's business. By their nature, forward-looking statements and forecasts involve risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. There are a number of factors that could cause actual results and developments to differ materially. For a discussion of those risks and uncertainties, please see the company's Annual Report/Form 20-F for 2005.
ZACTIMA(TM) is a trademark of the AstraZeneca group of companies.
