1 October 2019 - - British-Swedish biopharmaceutical company AstraZeneca has presented detailed overall survival results from the Phase III FLAURA trial of Tagrisso (osimertinib) in the 1st-line treatment of adult patients with locally-advanced or metastatic epidermal growth factor receptor -mutated non-small cell lung cancer (NSCLC), the company said.

Results showed a statistically significant and clinically meaningful improvement in OS, a key secondary endpoint for Tagrisso versus gefitinib or erlotinib, both of which were previous standard-of-care treatments in this setting (HR 0.799 [95% CI, 0.641-0.997], p=0.0462).

Tagrisso delivered a median OS of 38.6 months versus 31.8 months for the comparator arm. At three years, 28% of patients in the Tagrisso arm and 9% of patients in the comparator arm remained on 1st-line study treatment.

Tagrisso also showed a statistically significant and clinically meaningful 52% reduction in the risk of central nervous system disease progression, increasing the time patients with CNS metastases lived without CNS disease progression or death (HR 0.48 [95% CI, 0.26-0.86], p=0.014).

The results were presented at the presidential Symposium of the ESMO (European Society for Medical Oncology) 2019 Congress in Barcelona, Spain (Abstract #LBA5_PR).

In the FLAURA trial, the safety and tolerability of Tagrisso was consistent with its established profile. Tagrisso was generally well tolerated, with Grade 3 or higher adverse events occurring in 42% of patients taking Tagrisso versus 47% in the comparator arm.

The most common AEs in patients treated with Tagrisso were diarrhea, rash, nail toxicity, dry skin, stomatitis, fatigue and decreased appetite. Despite almost twice the length of therapy, fewer patients experienced a grade 3 or higher AE (42% vs. 47%) or discontinued due to AEs (15% vs. 18%).

The FLAURA trial met its primary endpoint in July 2017, showing a statistically significant and clinically meaningful improvement in PFS, increasing the time patients lived without disease progression or death from any cause.

Tagrisso is currently approved in 78 countries, including the US, Japan, China and the EU, for 1st-line EGFR-mutated (EGFRm) metastatic NSCLC.

Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitizing and EGFR T790M-resistance mutations, with clinical activity against CNS metastases.

Tagrisso 40mg and 80mg once-daily oral tablets have now received approval in more than 75 countries, including the US, Japan, China and the EU, for 1st-line EGFRm advanced NSCLC, and in more than 85 countries, including the US, Japan, China and the EU, for 2nd-line use in patients with EGFR T790M mutation-positive advanced NSCLC.

Tagrisso is also being developed in the adjuvant setting (ADAURA trial), in the locally-advanced unresectable setting (LAURA), in combination with chemotherapy (FLAURA2) in the metastatic setting, and with potential new medicines to address resistance to EGFR-TKIs (SAVANNAH, ORCHARD).

The FLAURA trial assessed the efficacy and safety of TAGRISSO 80mg orally once daily vs. comparator EGFR-TKIs (either gefitinib [250mg orally, once daily] or erlotinib [150mg orally, once daily]) in previously-untreated patients with locally-advanced or metastatic EGFRm NSCLC. The trial was double-blinded and randomized, with 556 patients across 29 countries.

AstraZeneca has a portfolio of approved and potential new medicines in late-stage clinical development for the treatment of different forms of lung cancer spanning several stages of disease, lines of therapy and modes of action.