Study published in the NEJM shows that oral Iressa (gefitinib) Provides Superior Efficacy Compared To Doublet Chemotherapy In Phase III First-Line Study In Non Small Cell Lung Cancer
MISSISSAUGA, ON, Aug. 19 /CNW/ - Data from the Phase III first-line IRESSA Pan-Asia Study (IPASS)(1), published today in The New England Journal of Medicine, demonstrated superior progression-free survival (PFS: the length of time a patient lives without their tumour growing) for the oral anti-cancer drug IRESSA, compared with intravenous carboplatin/paclitaxel chemotherapy in the overall population of clinically selected patients with advanced NSCLC in Asia (Hazard ratio (HR) 0.74, 95 per cent confidence interval (CI) 0.65 to 0.85, p less than 0.0001). This is the first time a targeted monotherapy has demonstrated significantly longer PFS than doublet chemotherapy.
The EGFR (epidermal growth factor receptor) mutation status of a patient's tumour was a strong predictor of benefit with IRESSA or chemotherapy. Pre-planned sub-group analyses showed that PFS was significantly longer for IRESSA than chemotherapy in patients with EGFR mutation positive tumours (HR 0.48, 95 per cent CI 0.36 to 0.64, p less than 0.0001), and significantly longer for chemotherapy than IRESSA in patients with EGFR mutation negative tumours (HR 2.85, 95 per cent CI 2.05 to 3.98, p less than 0.0001).
IRESSA also demonstrated significant benefits in response rates and offered a more favourable tolerability profile with superior quality of life improvement rates for patients versus chemotherapy.
IPASS was an open label, randomized, parallel-group study that assessed the efficacy, safety and tolerability of IRESSA versus carboplatin/paclitaxel as first-line treatment in a clinically selected population of patients from Asia. The primary endpoint of IPASS was PFS, with the objective of demonstrating that IRESSA was non-inferior to (at least as good as) carboplatin/paclitaxel doublet chemotherapy. The IPASS study exceeded its primary objective and demonstrated superiority of IRESSA relative to carboplatin/paclitaxel in terms of progression-free survival.
The study enrolled 1,217 patients in Asia with advanced NSCLC who had not received prior chemotherapy for advanced disease, whose tumours were of adenocarcinoma histology and who had either never smoked, or were former light smokers (ceased smoking at least 15 years ago and less than or equal to 10 pack-years exposure).
For secondary endpoints, objective response rate (ORR) was superior for IRESSA in the overall population (43 per cent vs. 32 per cent; p =0.0001); for patients with EGFR mutation positive tumours, ORR was superior for IRESSA (71.2 per cent vs. 47.3 per cent for IRESSA and carboplatin/paclitaxel respectively, p = 0.0001), and for patients with EGFR mutation negative tumours, ORR was superior for chemotherapy (1.1 per cent (one patient) vs. 23.4 per cent for IRESSA and carboplatin/paclitaxel respectively, p = 0.0013).
The safety profile of IRESSA was generally consistent with its prescribing information, previous IRESSA studies in the relapsed setting, and underlying disease. The most commonly reported adverse events with IRESSA are mild-to-moderate rash and diarrhea.
Lead Investigator, Professor Tony Mok (Hong Kong Cancer Institute, Chinese University of Hong Kong) said: "IRESSA is already an established therapy in Asia, including China and Japan, and is a proven valuable alternative to single agent chemotherapy in patients with pre-treated advanced NSCLC. Results from the IPASS study mean that IRESSA (a single once-daily oral tablet) offers a potential new standard of care in the first-line treatment of patients with EGFR mutation positive tumours."
In July 2009, the European Commission granted marketing authorization for IRESSA for the treatment of adults with locally advanced or metastatic NSCLC with EGFR mutation positive tumours across all lines of therapy. Outside of Europe, IRESSA is approved in 36 countries for the treatment of patients with locally advanced or metastatic NSCLC who have been pre-treated with chemotherapy. AstraZeneca is in consultation with relevant authorities around the world to discuss the potential use of IRESSA in first-line therapy.
In Canada, IRESSA was approved in late 2003 for third-line therapy of locally advanced or metastatic NSCLC. In 2006, it was restricted to only those patients already benefiting from IRESSA and whose tumours were EGFR expression status positive or unknown(2). The IPASS study results have been shared with Health Canada.
NOTES TO EDITORS
About IRESSA
- Mode of Action: IRESSA is an EGFR-TKI (epidermal growth factor
receptor-tyrosine kinase inhibitor), which targets and blocks the
activity of the EGFR-TK, an enzyme that regulates intracellular
signalling pathways implicated in cancer cell proliferation and
survival. Growth factor signalling has been identified as a key
driver of tumour growth and spread in a wide range of cancers.
- IRESSA (250 mg) is a once-daily oral therapy.
- IRESSA has a well-established, generally well-tolerated side effect
profile and is not typically associated with the cytotoxic side-
effects commonly seen with chemotherapy. The most commonly seen
side-effects of IRESSA are mild-to-moderate rash and
diarrhea(3),(4),(5).
- It is the only targeted therapy that has proven non-inferiority for
overall survival relative to chemotherapy in patients with pre-
treated advanced NSCLC(6).
To date, the number of patients who have taken IRESSA is over
300,000 around the world.
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(7).
- In 2009, an estimated 23,400 Canadians will be diagnosed with lung
cancer and 20,500 will die of it. Lung cancer remains the leading
cause of cancer death for both men and women(8).
- 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 per cent(9).
AstraZeneca on personalized healthcare
AstraZeneca is committed to the development of personalized healthcare (PHC) to improve clinical outcomes for patients. Approximately 10 per cent of AstraZeneca drug projects in clinical development are testing a PHC strategy and every new project carries out a systematic assessment to determine whether a PHC approach is appropriate. Linking therapies to diagnostics and tools may deliver superior outcomes through patient selection, improved dosing or disease definition. PHC requires knowledge of patients' individual characteristics and the way in which their disease has developed to deliver more effective therapy. AstraZeneca uses many technologies to predict biomarkers, including: gene expression, protein expression, gene sequence variation, tumour gene mutation, gene copy number and imaging.
About AstraZeneca Canada Inc.
AstraZeneca is a leading global pharmaceutical company with an extensive product portfolio spanning six major therapeutic areas: gastrointestinal, cardiovascular, infection, neuroscience, oncology, and respiratory. AstraZeneca's Canadian headquarters are located in Mississauga, Ontario, with a state-of-the-art drug discovery centre based in Montreal, Quebec. For more information, visit the company's website at www.astrazeneca.ca.
References
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(1) Mok TS, Wu Y-L, Thongprasert S, et al. Gefitinib or carboplatin-
paclitaxel in pulmonary adenocarcinoma. N Eng J Med 2009;
(2) AstraZeneca Canada Inc. Iressa Product Monograph.
http://www.astrazeneca.ca/documents/ProductPortfolio/IRESSA_PM_en.pdf
(3) Fukuoka M, Yano S, Giaccone G et al. Multi-institutional randomized
phase II trial of gefitinib for previously treated patients with
advanced non-small-cell lung cancer (The IDEAL 1 Trial) (corrected).
J Clin Oncol 2003;21(12):2237-2246.
(4) Kris MG, Natale RB, Herbst RS et al. Efficacy of gefitinib, an
inhibitor of the epidermal growth factor receptor tyrosine kinase, in
symptomatic patients with non-small cell lung cancer: a randomized
trial. JAMA 2003; 290(16):2149-2158.
(5) Frampton JE, Easthope SE. Gefitinib: a review of its use in the
management of advanced non-small-cell lung cancer. Drugs 2004;
64(21):2475-2492.
(6) Kim, ES et al. "Gefitinib versus docetaxel in previously treated
non-small-cell lung cancer (INTEREST): a randomized phase III
trial." The Lancet. 2008. 372: p.1809-1818.
(7) Ferlay, J. et al. GLOBOCAN 2002: Cancer Incidence, Mortality and
Prevalence Worldwide. IARC CancerBase No. 5. version 2.0. Lyon: IARC
Press, 2004.
(8) Canadian Cancer Society. Lung Cancer Statistics.
(9) Bepler G.Lung cancer epidemiology and genetics. J Thorac Imaging
1999; 14(4):228-234.
-30- /For further information: Stephanie Batcules,
Communications Manager, Oncology, AstraZeneca Canada, (905)
615-6849, stephanie.batcules@astrazeneca.com;
Lynn Bessoudo, Andrea Rosebrugh, NATIONAL Public Relations, (416)
848-1426, (416) 848-1456, lbessoudo@national.ca,
arosebrugh@national.ca/
Posted: August 2009
