Pivotal FLAURA study demonstrated 18.9 months median progression-free survival for patients receiving Tagrisso versus 10.2 months compared with earlier generation EGFR tyrosine kinase inhibitors
MISSISSAUGA, ON, July 12, 2018 – AstraZeneca Canada today announced that Health Canada has approved Tagrisso® (osimertinib) for the first-line treatment of patients with locally advanced (not amenable to curative therapies), or metastatic non-small cell lung cancer (NSCLC) whose tumours have epidermal growth receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations (either alone or in combination with other EGFR mutations). Tagrisso has been granted a Notice of Compliance under Priority Review status based on data from the phase III FLAURA trial, which showed that patients who received first-line treatment of Tagrisso demonstrated 18.9 months median progression-free survival (PFS) versus 10.2 months in patients receiving earlier generation first-line EGFR tyrosine kinase inhibitors (TKI) erlotinib or gefitinib.i In addition, preliminary overall survival (OS) data from the study indicated a 37 per cent reduction in the risk of death (Hazard Ratio [HR] 0.63 at 25% maturity, not statistically significant as the OS data is still immature).ii
Until now, Tagrisso was approved as the only second-line treatment for patients with EGFR mutated NSCLC that progressed on EGFR-TKI treatment and whose tumour tested positive for the EGFR T790M mutation, the most common mutation acquired by resistance to TKI therapy.
For many patients with advanced EGFR mutated NSCLC, their first treatment is their only treatment. Today’s announcement means that many more patients are now eligible to be treated earlier in their treatment journey with Tagrisso, a medicine that has been proven in a clinical study to provide almost nine months PFS benefits beyond that of earlier generation first-line EGFR TKI therapies.
More than half of all patients with EGFR mutated NSCLC will see the cancer spread to the central nervous system (CNS), including the brain, over the course of their disease. The development of CNS metastases leads to a poor prognosis and has a negative impact on quality of life. The FLAURA trial data demonstrated that PFS results for patients treated with first-line Tagrisso were consistent across all patient subgroups, including patients with or without CNS metastases. The FLAURA trial was the first and only study to demonstrate this level of efficacy in this difficult-to-treat patient population.iii
“The approval of Tagrisso in this first-line setting represents a major advancement in the treatment of EGFR mutated lung cancer,” said Dr. Glenwood Goss, Professor of Medicine, University of Ottawa, and Director of Clinical and Translational Research at the Ottawa Hospital Cancer Centre. “As an oncologist, I believe in using the best treatment first, and Tagrisso has shown to significantly extend progression-free survival and improve treatment of central nervous system metastases as a first-treatment of EGFR mutation positive non-small cell lung cancer. I am pleased to be able to offer this life-altering treatment as a first-line option to patients who need it.”
The Health Canada approval of Tagrisso is based on the results of the phase III FLAURA trial. The trial assessed the efficacy and safety of Tagrisso 80mg once daily compared to earlier generation first-line EGFR-TKIs in previously untreated patients with locally advanced or metastatic EGFR mutated NSCLC.iv The trial was double-blinded and randomized, with 556 patients across 29 countries and demonstrated a statistically significant and clinically meaningful median PFS, 18.9 months for Tagrisso vs. 10.2 months for comparator (HR 0.46; 95% confidence interval [CI] 0.37, 0.57; p<0.001).v
Safety data for Tagrisso were in line with those observed in prior clinical trials.vi The treatment was well tolerated, with grade 3 or higher adverse events (AEs) occurring in 34 per cent of patients taking Tagrisso vs 45 per cent in the comparator arm.vii The most common adverse reactions (≥20%) in patients treated with Tagrisso were diarrhea (58%), rash or acne (58%), dry skin (36%), paronychia (35%), decreased appetite (20%) and stomatitis (29%).viii
Detailed results from the FLAURA trial are published online in the New England Journal of Medicine.ix
“The approval of Tagrisso as a first-line treatment is welcome news for lung cancer patients, for whom every day counts,” said Shem Singh, Executive Director of Lung Cancer Canada. “Innovation in treatment offers hope against this difficult-to-treat disease and gives patients and their families a chance to spend more quality time together. This Health Canada approval is an important first step, and we call on all stakeholders to work together to ensure that Tagrisso in the first-line setting is publicly funded for all that need it.”
About Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the most commonly diagnosed cancer in Canada (excluding non-melanoma skin cancers), and the leading cause of death from cancer in Canada for both men and women.x On average, 78 Canadians are diagnosed with lung cancer every day and 58 Canadians will die from lung cancer each day.xi Lung cancer is a diverse disease which is often diagnosed at a late stage, making it difficult to treat.
There are two major types of lung cancer, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), which are determined by the type of cell in which the cancer starts.xii Non-small cell lung cancer is the most common form of lung cancer and accounts for 85 to 90 per cent of all lung cancers in Canada.xiii Often diagnosed in late stage, fewer than 17 per cent of patients with NSCLC will live more than five years following diagnosis.xiv Half of NSCLC cases are associated with known mutations.xv EGFR mutation occurs in approximately 10-35 per cent of NSCLC cases.xvi Most patients with EGFR mutated NSCLC progress following first-line treatment with approved TKIs within 9-12 months, due to acquired mutation resistance, of which the most common is EGFR T790M.xvii
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitising and EGFR T790M-resistance mutations, with clinical activity against CNS metastases. Tagrisso 40mg and 80mg once-daily oral tablets have been approved in Canada, the US, EU, Brazil and Russia for first-line EGFR mutated advanced NSCLC, and in more than 75 countries including Canada, the US, EU, Japan and China for patients in the second-line with EGFR T790M mutation-positive advanced NSCLC. Tagrisso is also being investigated in the adjuvant setting and in combination with other treatments.
Tagrisso was first approved with conditions by Health Canada (NOC/c) in July 2016 as the first and only medicine indicated for patients with locally advanced or metastatic EGFR T790M mutationpositive NSCLC. This was followed by a full approval as a second-line treatment in January 2018, based on the phase III AURA3 trial that demonstrated significant improvement in PFS with Tagrisso compared to chemotherapy.
In May 2017, Tagrisso in the second-line setting received a positive clinical recommendation for reimbursement by the pan-Canadian Oncology Drug Review (pCODR).
AstraZeneca is committed to working with the pan-Canadian Pharmaceutical Alliance (pCPA), provinces and territories to ensure that Tagrisso is made publicly available as soon as possible for appropriate patients in both the first and second-line settings. For patients, there is no time to wait.
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of primary and specialty care medicines that transform lives. Our primary focus is on three important areas of healthcare: Cardiovascular and Metabolic disease; Oncology; and Respiratory, Inflammation and Autoimmunity. AstraZeneca operates in more than 100 countries and its innovative medicines are used by millions of patients worldwide. In Canada, we employ more than 675 employees across the country and our AstraZeneca Canada headquarters are located in Mississauga, Ontario. For more information, please visit the company’s website at www.astrazeneca.ca.
Senior Manager, Corporate Communications, AstraZeneca Canada
Tel: 1-800-565-5877 x 45749
i AstraZeneca Canada Inc., Tagrisso® (osimertinib), Product Monograph. July 2018.
iii Soria J-C, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer. N Engl J Med. 2018;378:113-125
viii Soria J-C, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer. N Engl J Med. 2018;378:113-125
x Canadian Cancer Society. Lung Cancer Statistics. Accessed July 6, 2018. Available at: http://www.cancer.ca/en/cancerinformation/
xi Lung Cancer Canada, The Faces of Lung Cancer Report 2017. Accessed January 26, 2018. Available at:
xiii Molina JR, et al. Non-small cell lung cancer: Epidemiology, risk factors, treatment and survivorship. Mayo Clin Proc. 2008 May; 83(5):
xiv Lung Cancer Canada, The Faces of Lung Cancer Report 2017. Accessed January 26, 2018. Available at:
xv Savas P, Hughes B, Solomon B. Targeted therapy in lung cancer: IPASS and beyond, keeping abreast of the explosion of targeted
therapies for lung cancer. J Thorac Dis. Oct 2013;5 Suppl 5:S579-592.
xvi Dong, Lijun, Dan Lei, and Haijun Zhang. “Clinical Strategies for Acquired Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor
Resistance in Non-Small-Cell Lung Cancer Patients.” Oncotarget 8.38 (2017): 64600–64606. PMC. Accessed on June 20, 2018. Available at:
xvii Mazza, Valentina, and Federico Cappuzzo. “Treating EGFR Mutation Resistance in Non-Small Cell Lung Cancer – Role of Osimertinib.”
The Application of Clinical Genetics 10 (2017): 49–56. PMC. Accessed on June 20, 2018. Available at: