PHASE III STUDY DATA WITH VANDETANIB (ZACTIMA™) IN PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) PRESENTED AT AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Orlando FL, 30 May 2009 /PRNewswire/ — Data from the Phase III ZODIAC study in advanced non-small cell lung cancer patients, with the investigational drug vandetanib, were presented today at the American Society of Clinical Oncology (ASCO) meeting in Orlando. Results show that the study met its primary endpoint, demonstrating that the addition of vandetanib to docetaxel resulted in a statistically significant improvement in progression-free survival (PFS), the length of time a patient lives without their cancer growing (hazard ratio [HR] 0.79, 97.58% CI 0.70-0.90; P<0.001. Median PFS: 14.0 weeks vs. 17.3 weeks, favouring vandetanib). Vandetanib is the first oral targeted therapy to show evidence of clinical benefits when added to chemotherapy in a Phase III study in second line advanced NSCLC1.
ZODIAC is a randomized, double-blind, placebo-controlled Phase III study evaluating the combination of vandetanib 100mg with docetaxel versus docetaxel alone. The study enrolled 1391 patients previously treated with one prior anti-cancer therapy for advanced NSCLC.
Data from ZEAL2, a smaller Phase III study also featured on this year's ASCO program, are supportive of ZODIAC although the primary endpoint did not reach statistical significance in the ZEAL study (hazard ratio [HR] 0.86, 97.58% CI 0.69–1.06; P=0.108. Median PFS: 11.9 weeks vs. 17.6 weeks, favoring vandetanib). The combination of vandetanib plus pemetrexed did show a positive trend in prolongation of PFS compared with pemetrexed alone.
ZEAL is a randomized, double-blind, placebo-controlled Phase III study evaluating vandetanib 100mg plus pemetrexed versus pemetrexed alone. The study enrolled 534 patients previously treated with one prior anti-cancer therapy for advanced NSCLC.
Evaluation of secondary endpoints in the ZODIAC and ZEAL studies showed that the addition of vandetanib to chemotherapy significantly improved objective response rate, which is a measurement of tumor shrinkage (ZODIAC: 17% vs. 10%, P<0.001; ZEAL: 19.1% vs. 7.9%, P<0.001), the studies also showed that adding vandetanib to chemotherapy resulted in a significantly longer time to deterioration of disease related symptoms (ZODIAC: HR 0.78, P=0.002, FACT-L Lung Cancer Subscale; ZEAL: HR 0.61, P=0.004, Lung Cancer Symptom Scale). Overall survival in both studies showed a positive trend, although they did not reach statistical significance (ZODIAC Study: HR 0.91, 97.52% CI 0.78-1.07: P=0.196; ZEAL Study: HR 0.86, 97.54% CI 0.65-1.13; p=0.219).
The observed safety profile in both studies was consistent with previous studies with vandetanib in NSCLC. The most common adverse events associated with vandetanib included rash, diarrhea and hypertension (ZEAL); rash, diarrhea and neutropenia (low white blood cell count) (ZODIAC). Incidence of protocol-defined QTc prolongation was <2.0 percent in both studies and was not associated with symptoms.
"There are more deaths from lung cancer alone than from breast, colon, and prostate cancers combined - and it's extremely difficult to treat," said Professor Roy Herbst, M.D., Ph.D., The University of Texas M. D. Anderson Cancer Center, Texas, Principal Investigator on the ZODIAC study. "The ZODIAC study showed adding vandetanib to chemotherapy improved progression-free survival, in patients who have few, if any options for treatment."
Results from a third Phase III study, ZEST3, were also presented at this year's ASCO. While the primary objective of demonstrating a statistically significant prolongation of PFS for vandetanib was not met in this study, in a pre-planned non-inferiority analysis, vandetanib was shown to have similar efficacy to erlotinib for PFS and OS (PFS: hazard ratio [HR] 0.98, 95.22% CI 0.87–1.10; P=0.721; OS: HR 1.01, 95.08% CI 0.89–1.16; P=0.830). Objective response rate and symptom control were also similar for both treatments (ORR: both 12%; symptoms: pain, HR 0.96, P=0.583; dyspnea, HR 1.08, P=0.333; cough, HR 0.94, P=0.403).
The ZEST study was a randomized, double-blind, Phase III study evaluating the efficacy of vandetanib 300mg versus erlotinib 150mg. The study enrolled 1240 patients with locally advanced or metastatic NSCLC after failure of at least one prior anti-cancer therapy.
The most common adverse events observed in the ZEST study were rash, diarrhea and hypertension. Incidence of protocol-defined QTc prolongation was 5.1 percent in the vandetanib arm.
AstraZeneca plans to submit a regulatory submission for the use of vandetanib 100mg in combination with chemotherapy for patients with advanced NSCLC in the first half of 2009.
Evaluation of vandetanib is ongoing, as monotherapy or in combination with other anti-cancer therapies in a range of tumor types, including thyroid cancer.
Results from the ZEPHYR (300mg monotherapy study in EGFR failures in advanced NSCLC, Phase III) and ZETA (300 mg monotherapy in advanced medullary thyroid cancer, Phase III) studies will be available during the second half of 2009.
Full results from the Phase III studies will be presented at a media briefing on Saturday 30th May. For more details, please contact Emma Overington on email@example.com or +44 7971 769 239
ZACTIMA™ is a trademark of the AstraZeneca group of companies.
Notes To Editors
Vandetanib has a unique profile that fights cancer through two clinically proven mechanisms - by blocking the development of tumour blood supply (anti-angiogenesis or anti-VEGFR), and by blocking the growth and survival of the tumor itself (anti-EGFR). Vandetanib also inhibits RET-tyrosine kinase activity, an important growth driver in certain types of thyroid cancer.
About the Phase III studies in NSCLC
ZODIAC (ZACTIMA in cOmbination with Docetaxel In non-smAll cell lung Cancer) is a Phase III randomized, double-blind, placebo-controlled study evaluating the combination of vandetanib 100mg once daily plus docetaxel versus docetaxel alone in patients with locally advanced or metastatic NSCLC, treated with one prior anti-cancer therapy. It enrolled 1391 patients at 250 centers throughout Europe, North America, South America and Asia Pacific.
ZEAL (ZACTIMA Efficacy with Alimta in Lung cancer) is a randomized, double-blind, placebo-controlled Phase III study evaluating the combination of vandetanib 100mg with pemetrexed versus pemetrexed alone in patients with locally advanced or metastatic NSCLC, treated with one prior anti-cancer therapy. It enrolled 534 patients at 160 centers across 23 countries.
ZEST (ZACTIMA Efficacy Study versus Tarceva) is a Phase III randomized, double-blind, multi-centre study to assess the efficacy of vandetanib 300mg versus erlotinib in patients with locally advanced or metastatic NSCLC after failure of at least one prior anti-cancer therapy. It enrolled 1240 patients at 171 centers across 22 countries.
ZEPHYR (ZACTIMA Efficacy trial for NSCLC Patients with HistorY of EGFR-TKI and chemo-Resistance) is a Phase III, randomized, double-blind, parallel-group, multi-center study evaluating the efficacy of ZACTIMA 300mg plus best supportive care versus best supportive care in patients with locally advanced or metastatic (stage IIIB-IV) NSCLC after prior therapy with an EGFR inhibitor. The study is running in approximately 170 centers across 23 countries.
ZETA (Zactima Efficacy in Thyroid Cancer Assessment) is a phase III, randomized, double-blind, placebo-controlled, multi-centre study, evaluating once-daily ZACTIMA 300mg as a monotherapy in advanced medullary thyroid cancer.
About lung cancer
- Over 1.35 million new cases of lung cancer are diagnosed every year and nearly 1.2 million people die as a result of this devastating disease – more than breast, colon and prostate cancer combined4.
- Non-small cell lung cancer accounts for around 85% of all lung cancers5.
- If lung cancer is detected at early stages, before it has spread to other organs or lymph nodes, around half of patients can survive for five years or more. However, few lung cancers are found at this early stage and it is normally diagnosed at the advanced stage, when five year survival falls to approximately 15%6.
AstraZeneca is a major international healthcare business engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of US$ 31.6 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines. For more information about AstraZeneca, please visit: www.astrazeneca.com.
The statements contained herein include forward-looking statements. Although we believe our expectations are based on reasonable assumptions, any forward-looking statements, by their very nature, involve risks and uncertainties and may be influenced by factors that could cause actual outcomes and results to be materially different from those predicted. The forward-looking statements reflect knowledge and information available at the date of the preparation of this press release and the Company undertakes no obligation to update these forward-looking statements. Important factors that could cause actual results to differ materially from those contained in forward-looking statements, certain of which are beyond our control, include, among other things, those risk factors identified in the Company's Annual Report/Form 20-F for 2008. Nothing contained herein should be construed as a profit forecast.
- Herbst, R. et al. Vandetanib plus docetaxel vs docetaxel as 2nd-line treatment for patients with advanced non-small-cell lung cancer (NSCLC): a randomized, double-blind phase III trial (ZODIAC). ABS 31495. ASCO. 2009.
- De Boer, R. et al. Vandetanib plus pemetrexed vs pemetrexed as 2nd-line therapy in patients with advanced non-small-cell lung cancer (NSCLC): a randomized, double-blind phase III trial (ZEAL). ABS 31867, ASCO. 2009.
- Natale, R. et al. Vandetanib versus erlotinib in patients with advanced non-small-cell lung cancer (NSCLC) after failure of at least 1 prior cytotoxic chemotherapy: a randomized, double-blind phase III trial (ZEST). ABS 31610. ASCO. 2009.
- Ferlay, J. et al. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No. 5. version 2.0. Lyon: IARC Press, 2004.
- Ginsberg RJ. et al. Cancer: Principles and Practices of Oncology. 5th ed; 858-911. 1997. 6th ed. 925-983. 2001.
- Bepler G. Lung cancer epidemiology and genetics. J Thorac Imaging 1999; 14(4):228-234.