The European Commission ( EC ) has granted full marketing authorisation for Tagrisso ( Osimertinib ) 40mg and 80mg once-daily tablets for the treatment of adult patients with locally-advanced or metastatic epidermal growth factor receptor ( EGFR ) T790M mutation-positive non-small cell lung cancer ( NSCLC ).

The full approval for Tagrisso is based on the results of the phase III AURA3 trial. The EGFR T790M mutation can be detected with a validated test using either DNA derived from a biopsy or circulating tumour DNA ( ctDNA ) obtained from a plasma sample.

Data from AURA3 trial showed that Tagrisso demonstrated statistically-significant improvements in progression-free survival ( PFS ) over standard Platinum-based doublet chemotherapy in 419 patients with EGFR T790M-positive advanced NSCLC whose disease had progressed on or after EGFR TKI therapy.
Among patients taking Tagrisso, the progression-free survival was 10.1 months, compared to 4.4 months in the chemotherapy arm.
The objective response rate ( ORR ) was 71% compared to 31% for chemotherapy.
Among 144 patients with metastases to the central nervous system ( CNS ), progression-free surviavl was 8.5 months versus 4.2 months.

The most common adverse reactions in the Tagrisso group were diarrhoea ( 41% overall; 1% Grade greater than or equal to 3 ), rash (34% overall; 1% Grade greater than or equal to 3 ), dry skin ( 23% overall; 0% Grade greater than or equal to 3 ), paronychia ( 22% overall; 0% Grade greater than or equal to 3 ), stomatitis ( 15% overall; 0% Grade greater than or equal to 3, and pruritus ( 13% overall; 0% Grade greater than or equal to 3 ).

Warnings and precautions include interstitial lung disease ( ILD ), keratitis, left ventricular ejection fraction ( LVEF ) and QTc interval prolongation.

Tagrisso is a third generation, irreversible EGFR-TKI designed to inhibit both EGFR sensitising and EGFR T790M resistance mutations and to have activity in the CNS.

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths, more than breast, prostate and colorectal cancers combined.
Patients who have EGFRm NSCLC, which occurs in 10-15% of NSCLC patients in the US and Europe and 30-40% of NSCLC patients in Asia, are particularly sensitive to treatment with currently available EGFR-TKIs, which block the cell signalling pathways that drive the growth of tumour cells.
However, tumours almost always develop resistance to treatment, leading to disease progression.
Approximately two-thirds of patients develop resistance to approved EGFR-TKIs such as Gefitinib, Erlotinib and Afatinib due to the secondary mutation, T790M. ( Xagena )

Source: AstraZeneca, 2017