Phase III Studies Show That Vandetanib (Zactima) Brings Clinical Benefits to Patients With Lung Cancer
LONDON, Nov. 19, 2008-AstraZeneca today announced results from three Phase III studies of ZACTIMA (vandetanib) in combination with chemotherapy agents docetaxel (ZODIAC) and pemetrexed (ZEAL) and as monotherapy (ZEST) in non-small cell lung cancer (NSCLC).
Results from the ZODIAC and ZEAL studies showed advantages for vandetanib in combination with chemotherapy, compared to chemotherapy alone. The addition of vandetanib to chemotherapy prolonged Progression Free Survival (PFS), the primary endpoint, which achieved statistical significance in the larger ZODIAC study, but not in the smaller ZEAL study.
Clinical benefits were seen in secondary endpoints. Both studies showed that adding vandetanib to chemotherapy significantly improved Objective Response Rate (ORR), which is a measurement of tumour shrinkage. Additionally, positive trends in prolongation of Overall Survival (OS) were seen, although these did not reach statistical significance.
Importantly, the studies also showed that adding vandetanib to chemotherapy controlled the symptoms of lung cancer better than chemotherapy alone, allowing patients to maintain their quality of life for significantly longer.
ZODIAC is a randomised, 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.
ZEAL is a randomised, double-blind, placebo-controlled Phase III study evaluating the combination of vandetanib 100mg with pemetrexed versus pemetrexed alone. The study enrolled 534 patients previously treated with one prior anti-cancer therapy for advanced NSCLC.
ZEST, a randomised, double-blind, Phase III study evaluating the efficacy of vandetanib 300mg versus erlotinib 150mg, did not meet the primary objective of demonstrating a statistically significant prolongation of PFS for vandetanib. However, vandetanib and erlotinib showed equivalent efficacy for PFS and OS in a pre-planned non-inferiority analysis. The study enrolled 1240 patients with locally advanced or metastatic NSCLC after failure of at least one prior anti-cancer therapy.
The observed safety profile in these three Phase III studies was consistent with previous studies with vandetanib in NSCLC. The most common adverse events associated with vandetanib included rash, diarrhoea and hypertension.
John Patterson, Executive Director, Development, AstraZeneca commented: “Non-small cell lung cancer is a truly debilitating disease. These studies have shown that vandetanib can offer clinical benefit to patients with lung cancer by extending the time a patient can live with their cancer under control, while managing symptoms and maintaining quality of life better than chemotherapy alone.”
AstraZeneca plans to file a regulatory submission in the first half of 2009 following discussion with regulatory agencies. Full results from ZODIAC, ZEAL and ZEST will be presented at a forthcoming international medical congress.
Vandetanib is also currently being investigated in another Phase III monotherapy study in NSCLC (ZEPHYR) and in a number of other cancers, including thyroid cancer.
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 tumour 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
ZODIAC (ZACTIMA in cOmbination with Docetaxel In non-smAll cell lung Cancer) is a Phase III randomised, 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 centres throughout Europe, North America, South America and Asia Pacific.
ZEAL (ZACTIMA Efficacy with Alimta in Lung cancer) is a randomised, 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 approximately 160 centres across 23 countries.
ZEST (ZACTIMA Efficacy Study versus Tarceva) is a Phase III randomised, 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 approximately 171 centres across 22 countries.
ZEPHYR (ZACTIMA Efficacy trial for NSCLC Patients with HistorY of EGFR-TKI and chemo-Resistance) is a Phase III, randomised, double-blind, parallel-group, multi-centre 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 centres across 23 countries.
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 combined. Non-small cell lung cancer accounts for around 85% of all lung cancers. 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%.
AstraZeneca is a major international healthcare business engaged in research, development, manufacturing and marketing of prescription pharmaceuticals and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of US $29.55 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection product sales. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
For more information about AstraZeneca, visit www.astrazeneca.com
Neil McCrae +44 207 304 5045 (24 hours)
Chris Sampson +44 20 7304 5130 (24 hours)
Investor Enquiries UK:
Jonathan Hunt +44 207 304 5087 mob: +44 7775 704032
Mina Blair +44 20 7304 5084 mob: +44 7718 581021
Karl Hard +44 207 304 5322 mob: +44 7789 654364
Investor Enquiries US:
Ed Seage +1 302 886 4065 mob: +1 302 373 1361
Jorgen Winroth +1 212 579 0506 mob: +1 917 612 4043
Peter Vozzo (MedImmune) +1 301 398 4358 mob: +1 301 252 7518
Posted: November 2008