AstraZeneca

Preliminary Results of Ongoing Phase II Study Show Early Promise With ZD6474 (ZACTIMA[TM]) in a Rare Form of Thyroid Cancer

Alderley Park, England, November 16 (ots/PRNewswire) - - New Data Add Momentum to AstraZeneca's Novel Oncology Drug, ZD6474 (ZACTIMA[TM]), Which has Already Shown Promising Data in Non-Small Cell Lung Cancer (NSCLC) Preliminary results from a Phase II study showing promising clinical data with ZD6474 (ZACTIMA[TM]) in patients with a rare form of thyroid cancer(1) were presented during the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Philadelphia, USA, today. The study is an ongoing, single-arm investigation of ZD6474 in patients with hereditary medullary thyroid cancer. In addition to evaluating ZD6474 in thyroid cancer, AstraZeneca will begin recruitment into Phase III studies evaluating the anti-tumour activity of ZD6474 in advanced non-small cell lung cancer (NSCLC). Advanced hereditary medullary thyroid cancer, a rare malignancy, has a poor prognosis and there are currently very limited therapeutic options available. Initial data from the first 11 evaluable patients in this study (who received once daily treatment with ZD6474 300mg for at least three months) suggest promising clinical anti-tumour activity with ZD6474.(1) Of the patients assessed for tumour response, two experienced a partial response, where their measurable tumour shrank by 30% or more, and nine patients experienced stable disease, where the advancement of their cancer was halted.(1) These data also show that levels of plasma 'biomarkers' calcitonin and carcinoembryonic antigen - which generally reflect the amount of cancer in patients with medullary thyroid cancer - were reduced by an average of 72% and 25% respectively, following treatment with ZD6474.(1) This trial follows the recent announcement that the US Food and Drug Administration (FDA) has granted ZD6474 orphan drug designation for the investigation of rare forms of thyroid cancer. Lead trial investigator Professor Samuel Wells, MD, Duke University Medical Center, Durham NC, USA, commented, "These data are very encouraging for patients with this rare form of thyroid cancer. Neither standard chemotherapeutic regimens, nor radiation therapy, provide substantial benefits to these patients. In this small ongoing study, ZD6474 has shown promising results in patients with this disease." ZD6474 is a unique, once-daily oral therapy that selectively inhibits key signalling pathways involved in tumour growth and tumour blood supply, including RET kinase. RET kinase drives the growth and survival of certain tumours and is believed to be an important pathway in up to 40% of sporadic medullary thyroid cancer, and in up to 100% of hereditary medullary thyroid cancer cases.(2) It is estimated that 2-3% of the estimated 25,000 new cases of thyroid cancer diagnosed in the USA in 2005 are medullary thyroid cancer and of these, around a quarter are hereditary.(3) The incidence in the EU is similar. Professor Wells concluded, "ZD6474 is important because it targets more than one signalling pathway. Thus, a single pill administered orally has activity against different cellular processes needed by tumours to grow and spread." ZD6474 was generally well tolerated in the study. Side effects seen with ZD6474 include rash, nausea, diarrhoea, hypertension and asymptomatic QTc prolongation. ZACTIMA(TM) is a trademark of the AstraZeneca group of companies. Notes to Editors: Thyroid cancer - Thyroid cancer is a rare disease affecting approximately 290,000 people in the USA. Medullary thyroid cancer is a specific form of thyroid cancer that comprises 2-3% of the 25,000 new cases of the disease in the USA each year.(3) In approximately 40% of sporadic medullary thyroid cancer, and in up to 100% of hereditary medullary thyroid cancer cases, the cancer is caused by specific mutations in the RET proto-oncogene, a receptor tyrosine kinase, that transduces signals for cell growth and differentiation.(2) Neither standard chemotherapeutic regimens, nor radiation therapy, provide substantial benefits in patients with advanced hereditary medullary thyroid carcinoma. ZD6474 trial in thyroid cancer - The US Food and Drug Administration (FDA) granted ZD6474 orphan drug designation for the treatment of patients with follicular, medullary, anaplastic, and locally advanced and metastatic papillary thyroid cancer on 21 October 2005. AstraZeneca has also applied for orphan drug designation for ZD6474 in medullary thyroid cancer in Europe. - Trial 008 is an ongoing, open-label Phase II study evaluating the anti-tumour efficacy and safety of ZD6474 in patients with advanced hereditary medullary thyroid cancer.(1) Of the 11 patients available for evaluation of objective tumor response, two had a partial response (one patient developed a new tumour unrelated to thyroid cancer) and nine had stable disease (median 17 weeks; range: 12 to 31 weeks).(1) No patient experienced progressive disease, as would have been indicated by an increase in the size of metastatic medullary thyroid cancer.(1) ZD6474 Phase II studies in advanced NSCLC - The results of two Phase II NSCLC studies with ZD6474, Trials 003 and 006, were presented at the 11th World Conference on Lung Cancer (WCLC), July 2005 in Barcelona, Spain. Both studies met their primary endpoints.(4,5) - Trial 003, compared the anti-tumour effects of ZD6474 300mg monotherapy with gefitinib (IRESSA(R)) 250mg monotherapy in patients with advanced NSCLC. The results showed that patients receiving ZD6474 had a significant prolongation of progression free survival compared to gefitinib.(4) - Trial 006, compared the effects of a combination of ZD6474 100mg or 300mg plus docetaxel 75mg/m2 to docetaxel 75mg/m2 alone. Patients receiving ZD6474 100mg or 300mg plus docetaxel had an increased median progression free survival compared to docetaxel alone.(5) - In both trials (Trial 003 and Trial 006), 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.(4,5) Phase III studies evaluating the anti-tumour activity of ZD6474 in advanced non-small cell lung cancer (NSCLC) will further investigate the compound's impact on survival. ZD6474 (ZACTIMA[TM]) - ZD6474 is a unique once-daily oral therapy that selectively inhibits key signalling pathways involved in tumour growth including: vascular endothelial growth factor (VEGF) receptor signalling resulting in inhibition of tumour angiogenesis; and epidermal growth factor (EGF) receptor signalling, which may lead to direct inhibition of cancer cell proliferation and survival. - ZD6474 also inhibits RET kinase, which drives the growth and survival of certain tumours, is believed to be an important pathway in up to 40% of medullary thyroid cancer cases and in up to 100% of cases of hereditary medullary thyroid cancer.(2) 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 over US$21.4 billion and leading positions in sales of gastrointestinal, cardiovascular, respiratory, oncology and neuroscience products. In the United States, AstraZeneca is a US$9.6 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: www.astrazeneca.com References 1. Wells S et al. The Use of ZACTIMA(TM) (ZD6474) in the Treatment of Patients with Hereditary Medullary Thyroid Carcinoma. Presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, November 2005. 2. Gilliland FD, Hunt WC, Morris DM, Key CR (1997). Prognostic factors for thyroid carcinoma. A population-based study of 15,698 cases from the Surveillance, Epidemiology and End Results (SEER) program 1973 - 1991. Cancer, 79: 564-573. 3. National Cancer Institute. Genetics of Medullary Thyroid Cancer. http://www.cancer.gov/cancertopics/pdq/genetics/medullarythyr oid/healthprofes sional. Last accessed 05 October 2005. 4. Natale R et al. A comparison of the antitumour efficacy of ZD6474 and gefitinib (Iressa(TM)) in patients with NSCLC: results of a randomized, double-blind Phase II study. Lung Cancer 2005; 49 (Suppl 2): S36. 5. Herbst R et al. ZD6474 plus docetaxel in patients with previously treated NSCLC: results of a randomized, placebo-controlled phase II trial. Lung Cancer 2005; 49 (Suppl 2): S35. ots Originaltext: AstraZeneca Im Internet recherchierbar: http://www.presseportal.ch Contact: Contact Information Peter Edwards Global PR Manager - Oncology Shire Health International, Tel: +44(0)1625-232-685, Mobile: +44(0)7747-118-498, Peter.S.Edwards@astrazeneca.com; Catherine Hartley, Tel: +44(0)20-7108-6500, Mobile: +44(0)7789-008-047, Catherine.Hartley@shirehealthinternational.com

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