AstraZeneca gets USFDA priority review for Tagrisso plus chemotherapy for EGFR-mutated advanced lung cancer

The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance. The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is anticipated during the first quarter of 2024.

Each year, there are an estimated 2.2 million people diagnosed with lung cancer globally with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer. Approximately 70% of people are diagnosed with advanced NSCLC. Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said, “The FLAURA2 results reinforce Tagrisso as a backbone of standard of care in 1st-line EGFR-mutated non-small cell lung cancer, providing patients with an additional nine months of median progression-free survival when combined with chemotherapy. This option is particularly important for patients with a poorer prognosis such as those with brain metastases. We look forward to working with the FDA on an accelerated timeline to bring this treatment regimen to patients as quickly as possible.”

The sNDA is based on data from the FLAURA2 Phase III trial presented in a Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC).

In the trial, Tagrisso in combination with chemotherapy reduced the risk of disease progression or death by 38% compared to Tagrisso monotherapy, the 1st-line global standard of care (based on a hazard ratio [HR] of 0.62; 95% confidence interval [CI] 0.49-0.79; p<0.0001). By investigator assessment, the combination extended median PFS by 8.8 months versus Tagrisso alone. PFS results from blinded independent central review were consistent, showing Tagrisso plus chemotherapy extended median PFS by 9.5 months (based on HR of 0.62; 95% CI 0.48-0.80; p=0.0002).

Importantly, a clinically meaningful PFS benefit was observed across all prespecified subgroups, including patients with central nervous system metastases. In this group, the combination reduced the risk of disease progression or death by 53% compared to Tagrisso monotherapy (based on a HR of 0.47; 95% CI 0.33-0.66), extending median PFS by 11.1 months versus Tagrisso alone.

At the time of this analysis, the overall survival (OS) data were immature, however, a favourable trend was observed for Tagrisso plus chemotherapy. The trial continues to assess OS as a key secondary endpoint.

The safety profile of Tagrisso plus chemotherapy was generally manageable and consistent with the established profiles of the individual medicines. Adverse event rates were higher in the combination arm, driven by well-characterised chemotherapy-related adverse events. Additional safety information will be presented at a forthcoming medical meeting.

In August 2023, Tagrisso in combination with chemotherapy received Breakthrough Therapy Designation by the FDA in this setting for the 1st-line treatment of adult patients with locally advanced or metastatic EGFRm NSCLC.

Tagrisso is approved as monotherapy in more than 100 countries including in the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment of early-stage (IB, II and IIIA) EGFRm NSCLC.