Phase III FLAURA trial results show Tagrisso reduced the risk of progression or death by more than half, with consistent benefit across all subgroups, including patients with and without brain metastases
Unprecedented median progression-free survival (PFS) of 18.9 months compared with 10.2 months for the current standard of care
Clinically-meaningful preliminary overall survival benefit
MISSISSAUGA, ON, September 10, 2017 – AstraZeneca has presented the full results of the Phase III FLAURA trial, which support Tagrisso’s (osimertinib) clear potential as a new standard of care (SoC) in the first-line treatment of adult patients with locally-advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).1
Results of the Phase III FLAURA trial were included at the Presidential Symposium I of the European Society of Medical Oncology (ESMO) 2017 Congress in Madrid, Spain, and demonstrate a superior, clinically-meaningful PFS advantage with Tagrisso compared with current SoC EGFR-TKIs (erlotinib or gefitinib).1
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “The FLAURA data are truly exciting. Until now, even with the therapeutic advances offered by the first- and second-generation EGFR inhibitors, less than 20 per cent of EGFR mutation-positive NSCLC patients survive for five years. The FLAURA data suggest early and sustained benefit with Tagrisso that has the potential to significantly impact long-term patient outcomes and help address the considerable unmet need that remains.”
Dr. Suresh S. Ramalingam, Principal Investigator of the FLAURA trial, from the Winship Cancer Institute of Emory University, Atlanta, USA, said: “The FLAURA data for osimertinib are likely to result in a major paradigm shift in the treatment of patients with EGFR mutation-positive advanced lung cancer. Not only did the trial demonstrate a robust improvement in efficacy with osimertinib when compared to other commonly-used EGFR inhibitors, the side effects profile was also more favourable with osimertinib”.
“These new data from the FLAURA trial demonstrate the ongoing benefit of Tagrisso in providing a progression-free survival benefit over standard care and may provide physicians with a new first-line treatment option for those living with EGFR-mutated non-small cell lung cancer,” says Dr. Glenwood Goss, Professor of Medicine, University of Ottawa, and Director of Clinical and Translational Research at the Ottawa Hospital Cancer Centre. “In Canada, Tagrisso is already approved for use in the second-line setting, yet patients do not have public access to this new medicine. The FLAURA data provides further evidence of the benefits of this targeted therapy, underscoring why patients need access as soon as possible.”
Summary of key efficacy results:
Hazard ratio (HR)/
Odds ratio (OR)
|PFS (primary endpoint)||18.9 months (median)||10.2 months (median)||
95% CI, 0.37-0.57, p<0.0001
OS at 25% maturity
95% CI, 0.45-0.88, p=0.0068*
|Duration of Response (DoR)||17.2 months (median)||8.5 months (median)||N/A|
|Objective Response Rate (ORR)||80%||76%||
*0.0015 was the threshold required for statistical significance at the current level of maturity. A final OS analysis is planned at a later maturity.
Additional highlights from the FLAURA data include:
- Superior progression-free survival (PFS): Patients on Tagrisso had less than half the risk of progression or death compared with patients on erlotinib or gefitinib (hazard ratio [HR] 0.46; 95% confidence interval [CI] 0.37-0.57; p<0.0001). The median PFS was 18.9 months for patients on Tagrisso vs.10.2 months for patients in the comparator arm.
- Clinically-meaningful preliminary overall survival (OS) data at 25 per cent maturity: The hazard ratio for OS was 0.63 (95% CI: 0.45-0.88; p=0.0068) favouring Tagrisso. Overall survival data were 25 per cent mature at the time of the interim analysis (21% of the patients on Tagrisso had died and 30% of the patients on the comparator arm had died). The p-value of 0.0068 was not below the threshold of 0.0015 required for statistical significance at the current level of maturity. A final OS analysis is planned at a later maturity.
- PFS improvements consistent across subgroups: Improvements in PFS with Tagrisso were consistent across all pre-specified patient subgroups, with at least a 40 per cent reduction in the risk of progression or death, including in patients with/without central nervous system (CNS) metastases at study entry, Asian/non-Asian patients, patients with/without prior smoking history, and patients with exon 19 deletion/L858R.
- Impressive duration of response (DoR) and objective response rate (ORR): Patients treated with Tagrisso had more than double the median DoR than those on the comparator arm (17.2 months vs. 8.5 months), and an ORR (a measurement of tumour shrinkage) of 80 per cent vs. 76 per cent with the comparator arm (odds ratio 1.28 [0.85-1.93], p=0.2335).
The FLAURA safety data for Tagrisso were in line with those observed in prior clinical trials, with a low rate of Grade ≥3 adverse events (AEs). In patients treated with Tagrisso, the most common AEs were diarrhea (58% [2% Grade ≥3]) and dry skin (32% [<1% Grade ≥3]), and in the comparator arm group, the most common AEs were diarrhea (57% [3% Grade ≥3]) and dermatitis acneiform (48% [5% Grade ≥3]).1 Of the patients on Tagrisso, 33.7 per cent had a Grade ≥3 AE, compared with 44.8 per cent in the comparator arm, and 13.3 per cent of patients on Tagrisso had an AE leading to treatment discontinuation compared with 18.1 per cent in the comparator arm.1
AstraZeneca is in discussions with global health authorities regarding regulatory submissions for Tagrisso based on the FLAURA data. A status of regulatory submissions is usually provided with the Company’s quarterly results announcement.
Tagrisso is currently approved in more than 50 countries, including the US, EU, Japan and China, as second-line treatment for patients with advanced NSCLC who progress following treatment with an EGFR-TKI due to the EGFR T790M resistance mutation.
Notes to Editors
About Non-Small Cell Lung Cancer (NSCLC)
On average, 57 Canadians die from lung cancer every day – that’s more than 20,000 each year.2,3 In fact, more people die from lung cancer than breast cancer, colorectal cancer and prostate cancer combined.2 NSCLC is the most common form of lung cancer and accounts for 85 to 90 per cent of all lung cancers in Canada.4 Often diagnosed in late stage, fewer than 17 per cent of patients diagnosed with NSCLC will live more than five years following diagnosis.2 Ethnicity can increase risk for genetic mutations in NSCLC. In Caucasian populations, 10 to 15 per cent of all NSCLC diagnoses are EGFR mutation-positive, but this climbs to 30 to 40 per cent in people of Asian background with NSCLC.5 Also, NSCLC patients with the EGFR T790M mutation are more likely to be female and to have never smoked.6
FLAURA assessed the efficacy and safety of Tagrisso 80mg orally once daily vs. standard-of-care EGFR-TKIs (either erlotinib [150mg orally, once daily] or gefitinib [250mg orally, once daily]) in previously-untreated patients with locally-advanced or metastatic EGFRm NSCLC. The trial was a double-blinded, randomized study, with 556 patients across 30 countries.
The primary endpoint of the trial was PFS, and secondary endpoints included OS, ORR, DOR, disease control rate (DCR), safety, and measures of health-related quality of life (HRQoL).
Tagrisso 80mg once daily tablet is approved in Canada, the US, EU, Japan, Switzerland, Israel, Mexico, South Korea, Australia and a number of other countries as the first treatment for patients with locally-advanced or metastatic EGFR T790M mutation-positive NSCLC who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy. Eligibility for treatment with Tagrisso is dependent on confirmation that the patient has an EGFR T790M mutation.7 In Canada, Tagrisso received a Notice of Compliance with Conditions in July 2016.
Tagrisso has one of the fastest development programs, from start of clinical trials to approval, in just over two and a half years. Tagrisso is as an irreversible EGFR inhibitor, born out of scientific exploration and engineered to combat the mechanism of resistance by targeting the T790M resistance mutation.7 Tagrisso is also being investigated in the adjuvant and metastatic first-line settings, including in patients with and without brain metastases, in leptomeningeal disease, and in combination with other treatments.
About AstraZeneca in Lung Cancer
AstraZeneca is committed to developing therapies to help every patient with lung cancer. We have two approved therapies and a growing pipeline that targets genetic changes in tumour cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
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.
Michelle Marchione, Senior Manager, Corporate Communications AstraZeneca Canada
1 Ramalingam et al. Osimertinib vs standard-of-care EGFR-TKI as first-line treatment in patients with EGFRm advanced NSCLC: FLAURA. In: Presidential Symposium I of the European Society of Medical Oncology (ESMO) 2017 Congress; September 8 -12; Madrid, Spain.
2 Lung Cancer Canada. 2015 Faces of Lung Cancer Report. Available at: http://www.lungcancercanada.ca/getmedia/7f1ad2f4-2bb0-45e8-9bf5-d4fa01779a68/The-Faces-of-Lung-Cancer-2015.aspx. Accessed on September 8, 2017.
3 Canadian Cancer Society. Canadian Cancer Statistics 2017. Available at: http://www.cancer.ca/~/media/cancer.ca/CW/cancer%20information/cancer%20101/Canadian%20cancer%20statistics/Canadian-Cancer-Statistics-2017-EN.pdf?la=en.Accessed on September 8, 2017.
4 Molina JR, et al. Non-small cell lung cancer: Epidemiology, risk factors, treatment and survivorship. Mayo Clin Proc. 2008 May; 83(5): 584-594.
5 Ellison G, et al. EGFR mutation testing in lung cancer: a review of available methods and their use for analysis of tumour tissue and cytology samples. J Clin Pathol. 2013; 66: 79-89.
6 Gazdar A, et al. Hereditary lung cancer syndrome targets never smokers with germline EGFR gene T790M mutations. Thorac Oncol. 2014 April; 9(4): 456–463.
7 TAGRISSO™ (osimertinib) Product Monograph. Available at: https://www.astrazeneca.ca/content/dam/az-ca/downloads/productinformation/TAGRISSO%20-%20Product-Monograph.pdf. Accessed on September 8, 2017.