WILMINGTON, Del. & MADRID — (BUSINESS WIRE) — AstraZeneca today announced 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 1st-line treatment of adult patients with locally-advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).

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 progression-free survival (PFS) with osimertinib compared to current SoC EGFR tyrosine kinase inhibitors (TKIs) (erlotinib or gefitinib).

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% 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 study, from the Winship Cancer Institute of Emory University, Atlanta, GA, said: “The FLAURA data 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 favorable with osimertinib.”

Summary of key results:

*0.0015 was the threshold required for statistical significance at the current level of maturity. 
A final OS analysis is planned at a later stage.

Highlights from the FLAURA data presented include:

• Superior PFS (primary endpoint): Patients on osimertinib had less than half the risk of progression or death compared to 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 osimertinib vs. 10.2 months for patients in the comparator arm.
  
  
• Clinically meaningful preliminary overall survival (OS) data at 25% maturity: The hazard ratio for OS was 0.63 [95% CI: 0.45, 0.88; P=0.0068] favoring osimertinib. OS data were 25% mature at the time of the interim analysis. (21% of the patients on osimertinib 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 stage.
  
  
• PFS improvements consistent across subgroups: Improvements in PFS with osimertinib were consistent across all pre-specified patient subgroups, with at least a 40% 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 sensitizing mutations.
  
  
• Impressive duration of response (DoR) and objective response rate (ORR): Patients treated with osimertinib 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 tumor shrinkage) of 80% vs. 76% with the comparator arm [odds ratio 1.28 (0.85, 1.93), p=0.2335].

The FLAURA safety data for osimertinib was in line with that observed in prior clinical trials, with a low rate of Grade ≥3 adverse events (AEs). In patients treated with osimertinib, the most common AEs were diarrhea (58%, any grade [2% Grade ≥3]) and dry skin (32%, any grade [<1% Grade ≥3]), and in the comparator arm group the most common AEs were diarrhea (57%, any grade [2% Grade ≥3]) and dermatitis acneiform (48%, any grade [5% Grade ≥3]). Of the patients on osimertinib, 33.7% had a Grade ≥3 AE, compared to 44.8% in the comparator arm, and 13.3% of patients on osimertinib had an AE leading to treatment discontinuation compared to 18.1% in the comparator arm.

This indication is not yet FDA approved. AstraZeneca is in discussions with global health authorities regarding regulatory submissions for osimertinib based on the FLAURA data. A status of regulatory submissions is usually provided with the Company’s quarterly results announcement.

TAGRISSO once-daily tablets are approved by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after an EGFR TKI therapy. TAGRISSO is the first and only approved medicine in the US indicated for NSCLC patients who have tested positive for the EGFR T790M mutation.

TAGRISSO^® (osimertinib) Important Safety Information

• There are no contraindications for TAGRISSO
• Interstitial Lung Disease (ILD)/Pneumonitis occurred in 3.5% and was fatal in 0.6% of 833 TAGRISSO-treated patients. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms indicative of ILD (eg, dyspnea, cough, and fever). Permanently discontinue TAGRISSO if ILD is confirmed
• Heart rate-corrected QT (QTc) interval prolongation occurred in TAGRISSO-treated patients. Of the 833 TAGRISSO-treated patients, 0.7% of patients were found to have a QTc > 500 msec, and 2.9% of patients had an increase from baseline QTc > 60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
• Cardiomyopathy occurred in 1.9% and was fatal in 0.1% of 833 TAGRISSO-treated patients. Left Ventricular Ejection Fraction (LVEF) decline ≥ 10% and a drop to < 50% occurred in 4% of 655 TAGRISSO-treated patients. Conduct cardiac monitoring, including an assessment of LVEF at baseline and during treatment in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure or persistent, asymptomatic LV dysfunction that does not resolve within 4 weeks, permanently discontinue TAGRISSO
• Keratitis was reported in 0.7% of 833 TAGRISSO-treated patients in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, and/or red eye) to an ophthalmologist
• Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during TAGRISSO treatment and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
• The most common adverse reactions (≥20%) in patients treated with TAGRISSO were diarrhea (41%), rash (34%), dry skin (23%), nail toxicity (22%), and fatigue (22%)

Please see complete Prescribing Information including Patient Information.

Contacts
AstraZeneca
Michele Meixell or Alex Engel
Tel: +1 302 885 2677