AstraZeneca's supplemental New Drug Application (sNDA) for TAGRISSO® (osimertinib) in conjunction with chemotherapy received acceptance and been granted Priority Review in the US for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC).
The Food and Drug Administration (FDA) confers Priority Review to applications for pharmaceuticals that, if approved, would present significant enhancements over existing options by demonstrating superior safety or efficacy, preventing severe conditions, or improving patient adherence. The Prescription Drug User Fee Act date, signifying the FDA's deadline for regulatory decision, is expected in the first quarter of 2024.
Annually, an estimated 2.2 million individuals receive a lung cancer diagnosis globally, with 80-85% of cases being NSCLC, the predominant subtype. Approximately 70% of these cases are diagnosed at an advanced stage. Furthermore, about 10-15% of NSCLC patients in the US and Europe, and 30-40% in Asia exhibit EGFRm NSCLC.
Susan Galbraith, Executive Vice President of Oncology Research and Development at AstraZeneca, stated: “The FLAURA2 results solidify TAGRISSO's position as a cornerstone of first-line treatment for EGFR-mutated non-small cell lung cancer, affording patients an additional nine months of median progression-free survival when combined with chemotherapy. This option holds particular significance for patients with a graver prognosis, such as those with brain metastasis. We eagerly anticipate collaborating with the FDA on an expedited timeline to expedite the availability of this treatment regimen to patients.”
The sNDA draws on data from the FLAURA2 Phase III trial, which was presented in a Presidential Symposium at the 2023 World Conference on Lung Cancer organized by the International Association for the Study of Lung Cancer (IASLC).
In the trial, the combination of TAGRISSO with chemotherapy reduced the risk of disease progression or mortality by 38% compared to TAGRISSO monotherapy, the established global first-line 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 prolonged median PFS by 8.8 months relative to TAGRISSO alone. PFS findings from blinded independent central review were congruent, indicating that TAGRISSO in combination with chemotherapy extended median PFS by 9.5 months (based on HR of 0.62; 95% CI 0.48-0.80; p=0.0002).
Notably, a clinically significant PFS benefit was observed across all predefined subgroups, including patients with central nervous system metastasis. In this subgroup, 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 inconclusive; however, a favorable trend was evident for TAGRISSO plus chemotherapy. The trial continues to evaluate OS as a critical secondary endpoint.
The safety profile of TAGRISSO in combination with chemotherapy was generally manageable and aligned with the established profiles of the individual drugs. Adverse event rates were higher in the combination arm, primarily driven by well-characterized chemotherapy-related adverse events. Further safety details will be presented at an upcoming medical conference.
In August 2023, TAGRISSO in combination with chemotherapy received Breakthrough Therapy Designation from the FDA for this setting in the first-line treatment of adult patients with locally advanced or metastatic EGFRm NSCLC.
TAGRISSO is sanctioned as a monotherapy in over 100 countries, including the US, EU, China, and Japan. Approved indications encompass first-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.