Tagrisso Receives Full FDA Approval for Lung Cancer

Only medication indicated for NSCLC with EGFR T790M mutation

The FDA has granted full approval for osimertinib (Tagrisso, AstraZeneca) 80-mg 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 during or after EGFR tyrosine kinase inhibitor (TKI) therapy. Osimertinib is the only approved medication in the United States indicated for NSCLC patients who have tested positive for the EGFR T790M mutation.

The full approval was based on data from the phase 3 AURA3 trial, in which osimertinib significantly improved progression-free survival (PFS) compared with platinum-based doublet chemotherapy, providing 10.1 months of median PFS compared with 4.4 months with chemotherapy (hazard ratio, 0.30; 70% risk reduction; P < 0.001). The results of this study were published in the New England Journal of Medicine.

The most common adverse events among osimertinib-treated patients included diarrhea (41%), rash (34%), dry skin (23%), nail toxicity (22%), and fatigue (22%). Dose reductions were necessary in 2.9% of patients treated with osimertinib. The most frequent adverse events leading to dose reductions or interruptions included prolongation of the QT interval (1.8%), neutropenia (1.1%), and diarrhea (1.1%). Serious adverse events were reported in 18% of patients treated with osimertinib and in 26% of patients in the chemotherapy group.

Osimertinib was granted fast track, breakthrough therapy, and priority review designations by the FDA. The drug received accelerated approval for its current indication in 2015, based on the tumor response rate and the duration of response.

Eligibility for treatment with osimertinib depends on confirmation that the EGFR T790M mutation is present in the tumor.

Osimertinib is a third-generation, irreversible EGFR TKI designed to inhibit both EGFR-sensitizing and EGFR T790M resistance mutations and to have activity in the central nervous system (CNS). Osimertinib is also being investigated in the adjuvant and metastatic first-line settings, including in patients with and without CNS metastases, in those with leptomeningeal metastases, and in combination with other treatments.

Source: AstraZeneca; March 31, 2017.