Targeted approach represents paradigm shift in the diagnosis and treatment of
non-small cell lung cancer (NSCLC)

With a recent Health Canada approval for IRESSA(R), Canadian lung cancer patients can now be tested for EGFR mutation status and be treated with a more effective and better tolerated alternative to chemotherapy, as a first-line therapy

MISSISSAUGA, ON, March 16 /CNW/ - AstraZeneca Canada announces the recently approved indication for IRESSA(R), a once-daily oral targeted therapy for the first-line treatment of patients with locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC) who have activating mutations of the epidermal growth factor receptor-tyrosine kinase (EGFR-TK).(1) In conjunction with this approval, AstraZeneca is also announcing the availability of a diagnostic test which can now determine a patient's EGFR mutation status, representing a new era in personalized lung cancer treatment in Canada.

In a recent clinical trial, IRESSA had a response rate of over 70 per cent for NSCLC patients who were identified as EGFR mutation positive.(2) Approximately 10 per cent of non-Asian NSCLC patients and approximately 40 per cent of Asian NSCLC patients have EGFR mutation-positive tumours.(1) These mutations are more commonly observed in never-smokers, patients with adenocarcinoma histology, females and those of Asian origin.(1) Patients with EGFR mutation-negative NSCLC have been shown to respond better to first-line treatment with standard chemotherapy.(2)

"IRESSA, in conjunction with EGFR mutation testing, represents an important step forward in the treatment of this devastating disease," said Dr. Glenwood Goss, Head, Medical Oncology, Ottawa Hospital Cancer Centre. "For the first time, Canadian patients with EGFR mutation-positive advanced NSCLC will have a more effective and better tolerated first-line treatment alternative to chemotherapy, bringing clarity and peace of mind."

Through genetic testing, physicians can now identify which of the distinct EGFR gene mutations their patients have (mutation-positive or mutation-negative) and determine the most appropriate first-line therapy. This shift to a personalized care model allows oncologists to select treatments according to who will benefit. This model will ultimately reduce the risk of progression and positively impact quality of life and symptom control for specific lung cancer patients.

AstraZeneca Assists with EGFR Testing for Canadians

AstraZeneca Canada will fund testing and drug access through the IRESSA Alliance Program established to assist eligible patients. This program will be available on an introductory basis prior to public and private coverage. AstraZeneca is currently developing a website on EGFR mutation status for physicians and patients with lung cancer, as well as a site to support patients on IRESSA. All newly diagnosed NSCLC patients should speak with their physician about testing to understand their options for mutation status testing.

"Understanding how lung cancer is treated can be confusing for patients when they are first diagnosed," said Catherine Black of Lung Cancer Canada. "But now, with this targeted approach to lung cancer care, patients in partnership with their physician, can have confidence that they are selecting the right treatment based on their particular tumour type."

"To be diagnosed with lung cancer is terrifying," said Roz Brodsky. "As a five year survivor, I am thrilled that we now have more tools available that will ensure people get the right treatment for their particular type of lung cancer. Targeted therapies like IRESSA offer new hope to so many in their fight against lung cancer."

About the IPASS Study

IRESSA's approval was based on the IPASS study (IRESSA Pan-ASia Study), published last year in The New England Journal of Medicine. 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.(2) The primary endpoint of IPASS was PFS (or progression free survival which is the length of time patients live without their tumour progressing), with the objective of demonstrating that IRESSA was non-inferior to carboplatin/paclitaxel doublet chemotherapy.(2)

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).(2)

The IPASS study demonstrated that in the sub-group of patients who were EGFR mutation positive, PFS was significantly longer for IRESSA versus carboplatin/paclitaxel (n=261, HR 0.48, 95% CI, 0.36 to 0.64; p(less than)0.001); in other words it reduced the risk of progression by 52 per cent and extended the median time to progression by 3.2 months beyond what was shown with standard chemotherapy (9.5 months vs. 6.3 months).(1),(2) As well, in EGFR mutation-positive patients, IRESSA had a more favourable tolerability profile, and demonstrated a significant improvement in quality of life and lung cancer symptoms vs. carboplatin/paclitaxel.(2)

Recently the American Society of Clinical Oncology (ASCO) clinical practice guidelines for the treatment of patients with stage IV NSCLC were updated and support the use of IRESSA as a first-line treatment for patients with EGFR mutation-positive advanced NSCLC.(3)

About Lung Cancer

Lung cancer remains the leading cause of cancer death for both men and women in Canada.(4) In 2009, an estimated 23,400 Canadians were diagnosed with lung cancer and 20,500 died of it. In Canada, one in 11 men is expected to develop lung cancer during his lifetime and one in 13 will die of it. One in 16 women is expected to develop lung cancer during her lifetime and one in 18 is expected to die of it.(4)

About IRESSA

IRESSA is an EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor) which targets and blocks the activity of the enzyme that regulates cancer cell proliferation and survival.(1) 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.(1) In Canada, IRESSA was first approved in December 2003 for the third-line therapy of locally advanced or metastatic NSCLC. In June 2006, the use of IRESSA was restricted by Health Canada to only those patients already benefiting from it and whose tumours were EGFR expression status positive or unknown following data from the Phase III international study, Iressa Survival Evaluation in Lung Cancer (ISEL), in pre-treated patients not eligible for further chemotherapy.

ISEL did not meet its primary objective of a statistically significant improvement in overall survival for IRESSA compared to placebo, but did confirm a number of important clinical benefits for IRESSA including tumour shrinkage and a significant improvement in time to treatment failure.(5)

The refractory nature (meaning patients whose tumours had grown during or soon after receiving prior chemotherapy) of the ISEL population is the most likely explanation for the magnitude of the survival improvement with IRESSA compared to placebo not reaching statistical significance.

The IPASS data was then published in August 2009 and demonstrated clinical significance for a sub-population of patients.(2) This study was submitted to Health Canada which led to the approval of the new indication on December 18, 2009.

"IRESSA's approval is the result of our perseverance and commitment to patients and medical discovery," said Marc Zarenda, Scientific Director, AstraZeneca Canada. "We experienced challenges, but forged ahead to understand why certain patients seemed to respond particularly well to IRESSA. We are so pleased that this new indication will provide access to a subgroup of NSCLC patients and introduce a truly personalized approach to treating lung cancer."

AstraZeneca Oncology and Personalized Healthcare

AstraZeneca Oncology is committed to the discovery and development of new and effective agents for preventing and treating cancer. A number of AstraZeneca's research compounds are targeting various signalling processes which are critical to cancer cell division and survival including anti-angiogenesis and inhibition of DNA repair. In meeting this challenge, AstraZeneca seeks to improve patient prognosis, prolong survival and improve quality of life.

AstraZeneca recognizes the increasing potential and importance of science-driven patient selection strategies that offer the possibility of enhanced clinical benefit or improved safety profile for all therapeutic agents - personalized healthcare (PHC). PHC has become a fundamental component of drug discovery and development today, and AstraZeneca has taken positive steps to ensure that all novel drug development projects establish appropriate PHC plans based on the current state of the science and clinical understanding. AstraZeneca is continuously building on its established strengths with the goal of becoming the company that that people turn to for better treatments to fight cancer.

About AstraZeneca

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.ca

    
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    References

    (1) IRESSA(R) Canadian Product Monograph. AstraZeneca Canada. 2009.
    (2) Mok T et al. Gefitinib or carboplatin-paclitaxel in pulmonary
        adenocarcinoma. New England Journal of Medicine: 361 (10):947-957.
        2009.
    (3) Azzoli G et al. American Society of Clinical Oncology Clinical
        Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell
        Lung Cancer. Last accessed December 22, 2009 at:
        http://www.asco.org/guidelines/nsclc
    (4) Canadian Cancer Society. Lung Cancer Statistics. Last accessed
        December 17, 2009 at:
   
http://www.cancer.ca/canada-wide/about%20cancer/cancer%20statistics/stats%20at%20a%20glance/lung%20cancer.aspx?sc_lang=en
    (5) Price, N. Clinical development of Gefitinib in Non-Small-Cell Lung
        Cancer and the Iressa Survival Evaluation in Lung Cancer Trial.
        Clinical Lung Cancer: January 2009.
    

IRESSA(R) is a trade-mark of the AstraZeneca group of companies.

For further information: Stephanie Batcules, Communications Manager, Oncology, AstraZeneca Canada, [phone], [email protected]; Elisabeth Mozel-Jury, Lynn Bessoudo, NATIONAL Public Relations, [phone], [phone], [email protected], [email protected]