Results from a prespecified exploratory analysis of the FLAURA2 Phase III trial showed AstraZeneca’s Tagrisso (osimertinib) with the addition of chemotherapy demonstrated a 42% improvement in central nervous system (CNS) progression-free survival (PFS), compared to Tagrisso alone for patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) and brain metastases at baseline, representing 40% of patients in the trial, as assessed by blinded independent central review (BICR).

These results were presented today in an oral presentation at the European Society for Medical Oncology (ESMO) Congress in Madrid, Spain (abstract #LBA68).

In this group of patients, Tagrisso with the addition of chemotherapy reduced the risk of CNS disease progression or death by 42% compared to Tagrisso alone (based on a hazard ratio [HR] of 0.58; 95% confidence interval [CI] 0.33-1.01) as assessed by BICR. With two years of follow-up, 74% of patients treated with Tagrisso plus chemotherapy had not experienced CNS disease progression or death versus 54% of patients treated with Tagrisso monotherapy. Results also showed a higher proportion of patients demonstrated CNS complete response (CR) with Tagrisso plus chemotherapy (59%) versus Tagrisso alone (43%).

David Planchard, MD, PhD, thoracic oncologist at Gustave Roussy Institute of Oncology and principal investigator for the trial, said: “Osimertinib has a proven ability to cross the blood-brain barrier and improve outcomes for patients with lung cancer and central nervous system metastases, who often face a poorer prognosis than patients whose disease has not spread to the brain. In FLAURA2, the addition of chemotherapy to osimertinib led to a complete response and the disappearance of these tumours in the brain, in more than half of these patients.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “In this trial, patients with brain metastases at baseline saw a meaningful benefit with the FLAURA2 regimen, offering hope for patients whose cancer has spread to the brain. These data build on the recent positive progression-free survival results from FLAURA2, further reinforcing Tagrisso as the backbone therapy in EGFR-mutated non-small cell lung cancer.”

The safety profile of Tagrisso with the addition of chemotherapy was generally manageable and consistent with the established profiles of the individual medicines. Adverse event (AEs) rates were higher in the Tagrisso plus chemotherapy arm, driven by well-characterised chemotherapy-related AEs. Tagrisso discontinuation rates were low in both arms of the trial (11% for the Tagrisso plus chemotherapy arm and 6% for the monotherapy arm).

In the Tagrisso plus chemotherapy arm, patients remained on Tagrisso for a median duration of 22.3 months, while patients had a median exposure to platinum-based chemotherapy of 2.8 months and a median exposure to pemetrexed of 8.3 months.

Summary of results: FLAURA2 CNS efficacyi

 Tagrisso plus chemotherapy(n=118)Tagrisso monotherapy(n=104)
PFS HR (95% CI)0.58 (0.33-1.01)
Median PFS (months; 95% CI)30.2 (28.4-NCii)27.6 (22.1-NC)
CNS objective response rate, n (%)86 (73)72 (69)
CR, n (%)70 (59)45 (43)
Median CNS duration of response (in months; 95% CI)NRiii (23.8-NC)26.2 (19.4-NC)

i The data cut-off date was 3 April, 2023. 
ii NC, non-calculable
iii NR, not reached

Earlier this month, Tagrisso with the addition of chemotherapy was granted Priority Review by the Food and Drug Administration (FDA) for the 1st-line treatment of adult patients with locally advanced or metastatic EGFRm NSCLC based on positive PFS data from the FLAURA2 Phase III trial recently presented at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer. In August 2023, Tagrisso with the addition of chemotherapy also received Breakthrough Therapy Designation from the FDA in this setting.