February 07, 2016 – The European Commission has approved once-daily Osimertinib (Tagrissa) for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) that is positive for the epidermal growth-factor receptor (EGFR) T790M mutation. This follows a positive review in December 2015. Previously, in November 2015, the American Food and Drug Administration (FDA) had also approved Osimertinib (Tagrissa) for
the same indication, based on the same early clinical trial data.
To be eligible for Osimertinib (Tagrissa) treatment, patients must undergo diagnostic testing that uses either tumor tissue or plasma to establish the presence of the T790M mutation. In fact, nearly two-thirds of patients with NSCLC whose disease progresses after treatment with an EGFR tyrosine kinase inhibitor (TKI) develop the T790M mutation, according to a company statement. In addition, a small number of patients (3% to 5%) have the T790M mutation at NSCLC diagnosis. Once patients harbor this mutation, they will not respond to treatment with an EGFR TKI.
Osimertinib (Tagrissa) is indicated for patients with T790M mutation-positive NSCLC, whether or not they have been previously treated with a TKI. Osimertinib (Tagrissa) targets both the EGFR mutation that triggers the cancer development and the T790M mutation. The new approval for Osimertinib (Tagrissa) is based on data from two phase 2 studies (AURA extension and AURA2) and the AURA phase 1 expansion study, which together demonstrated efficacy in 474 patients with EGFR T790M-mutation NSCLC who had progressed on or after an EGFR TKI.
In the combined phase 2 studies, the objective response rate was 66%; in the phase 1 study, the rate was 62%. Progression-free survival was 9.7 months in the combined phase 2 studies and 11.0 months in the phase 1 study. Median duration of response was not reached in the combined phase 2 studies and was 9.7 months in the phase 1 study.
The most common adverse events in the two AURA phase 2 studies included diarrhea (all grades, 42.0%; grade 3/4, 1.0%), rash (all grades, 41.0%; grade 3/4, 0.5%), dry skin (all grades, 31.0%; grade 3/4, 0.0%), and nail toxicity (all grades, 25.0%; grade 3/4, 0.0%). Warnings and precautions include interstitial lung disease and QT interval prolongation.
Osimertinib (Tagrissa) was reviewed and approved under the European Medicine Agency’s accelerated assessment program. The conditional approval is based on response-rate data. The manufacturer must eventually provide data from an ongoing phase 3 study.
“Osimertinib defines a new generation of targeted EGFR TKI treatments, and the European Commission’s expedited approval reflects the importance of this innovative medicine for addressing the needs of patients with lung cancer who have the T790M mutation,” Sean Bohen, MD, PhD, chief medical officer at AstraZeneca, the maker of Osimertinib (Tagrissa), said in a press statement.