The FDA ( Food and Drug Administration ) has granted full approval for Tagrisso ( Osimertinib ) 80mg once-daily tablets, for the treatment of patients with metastatic epidermal growth factor receptor ( EGFR ) T790M mutation-positive non-small cell lung cancer ( NSCLC ), as detected by an FDA-approved test, whose disease has progressed on or after an EGFR tyrosine kinase inhibitor ( TKI ) therapy.
Tagrisso is the first and only approved medicine in the US indicated for NSCLC patients who have tested positive for the EGFR T790M mutation, and efficacy data suggest it may be a new standard of care for these patients.
The full approval in the US is based on data from the randomised, phase III AURA3 trial, in which Tagrisso significantly improved progression-free survival ( PFS ) versus Platinum-based doublet chemotherapy, providing 10.1 months of median PFS compared to 4.4 months from chemotherapy ( hazard ratio, HR=0.30; 70% risk reduction; 95% Confidence Interval [ CI ]: 0.23; 0.41; P less than 0.001 ).
In AURA3 the most common ( more than 20% ) adverse reactions observed in Osimertinib-treated patients were diarrhea ( 41% ), rash ( 34% ), dry skin ( 23% ), nail toxicity ( 22% ), and fatigue ( 22% ).
Dose reductions occurred in 2.9% of patients treated with Osimertinib.
The most frequent adverse reactions that led to dose reductions or interruptions were prolongation of the QT interval as assessed by ECG ( 1.8% ), neutropenia ( 1.1% ), and diarrhea ( 1.1% ).
Serious adverse reactions were reported in 18% of patients treated with Osimertinib and 26% of patients in the chemotherapy group.
No single serious adverse reaction was reported in 2% or more patients treated with Osimertinib.
Tagrisso 40 mg and 80 mg once daily oral tablet has been approved in over 45 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced non-small cell lung cancer ( NSCLC ).
Eligibility for treatment with Tagrisso is dependent on confirmation that the EGFR T790M mutation is present in the tumour.
Osimertinib is a third generation, irreversible EGFR tyrosine kinase inhibitor designed to inhibit both EGFR sensitising and EGFR T790M resistance mutations and to have activity in the central nervous system ( CNS ).
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths and more than breast, prostate and colorectal cancers combined.
Among patients with NSCLC, 20% to 40% have brain metastases at some time during the course of their disease.
Patients who have the EGFRm form of 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 and Erlotinib due to the secondary mutation, T790M. ( Xagena )
Source: AstraZeneca, 2017