Combination shows consistent benefit across prespecified post-progression outcomes.

Results from the FLAURA2 Phase III trial showed AstraZeneca's ​Tagrisso (osimertinib) with the addition of chemotherapy​ provided a clinically meaningful and consistent benefit in subsequent outcomes after disease progression in patients with locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). Tagrisso with the addition of chemotherapy also demonstrated a favourable trend toward overall survival (OS) improvement at two years of follow up. These results were presented today at the 2024 European Lung Cancer Congress (ELCC) in Prague, Czech Republic (abstract #4O).

This follows primary endpoint data presented at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC) and published in The New England Journal of Medicine, which showed Tagrisso with the addition of chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS). In February 2024, Tagrisso with the addition of chemotherapy was approved in the US following a Priority Review by the Food and Drug Administration (FDA) based on these results.

At 41% data maturity, the OS interim results showed a favourable trend with the Tagrisso plus chemotherapy arm (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.57-0.97), with consistent results across prespecified subgroups, including sex, race, type of EGFR mutation, age at time of diagnosis, smoking history, performance status and central nervous system (CNS) metastases status at baseline. The OS data were not statistically significant at this interim analysis and will continue to be assessed as a key secondary endpoint at final analysis.

Tagrisso with the addition of chemotherapy also showed a consistent benefit across prespecified post-progression endpoints of time to first subsequent treatment (TFST; HR 0.73; 95% CI 0.56-0.94), time to progression on 2nd-line therapy (PFS2; HR 0.70; 95% CI 0.52-0.93) and time to second subsequent treatment (TSST; HR 0.69; 95% CI 0.51-0.93).

Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer Institute and principal investigator for the trial, said: "The improvement in post-progression outcomes with chemotherapy added to standard-of-care osimertinib is encouraging for patients with advanced EGFR-mutated lung cancer, particularly the encouraging trend toward overall survival. These results further validate the importance of this additional treatment option, especially for those patients whose cancer has spread to the brain, those with L858R mutations, or other cause for poorer prognosis."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "FLAURA2 reinforces Tagrisso as the backbone therapy in EGFRm non-small cell lung cancer either as monotherapy or in combination with chemotherapy, delivering the longest reported progression-free survival benefit in the 1st-line advanced setting. We're excited to see a favourable trend toward overall survival and look forward to seeing this data mature over time."

Summary of key post-progression results: FLAURA2

Additional safety analyses from the FLAURA2 trial were also presented at ELCC (abstract #10P). Results showed adverse event onset frequency and severity were highest following initial chemotherapy added to Tagrisso and reduced over time during the maintenance period.

An analysis of patient-reported outcomes from the FLAURA2 trial was also presented at ELCC (abstract #9P). Results showed a trend toward improved health-related quality of life (HRQoL) and a trend toward improvement in several symptoms following chemotherapy added to Tagrisso. Symptoms included dyspnoea (shortness of breath or breathlessness), chest pain and cough. Any decline in HRQoL from adding chemotherapy to Tagrisso was not clinically meaningful and was temporary, resolving after chemotherapy was completed.

Tagrisso is also 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 EGFRm NSCLC. Regulatory applications are under review in several countries based on the FLAURA2 Phase III results.

As part of AstraZeneca's ongoing commitment to treating patients as early as possible in lung cancer, Tagrisso is also being investigated in the neoadjuvant setting in the NeoADAURA Phase III trial with results expected later this year, and in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial. Each of these Phase III trials serves to reinforce the proven benefit of Tagrisso in the early-stage setting.