The FDA has granted a breakthrough therapy designation to osimertinib (Tagrisso, AstraZeneca) for the first-line treatment of patients with metastatic epidermal growth factor receptor (EGFR) mutation-positive non–small-cell lung cancer (NSCLC).
The FDA granted the designation based on data from the phase 3 FLAURA trial of osimertinib versus standard-of-care EGFR tyrosine kinase inhibitor (TKI) therapy in previously untreated patients with locally advanced or metastatic EGFR mutation-positive NSCLC. In the trial, median progression-free survival was 18.9 months for osimertinib compared with 10.2 months for EGFR-TKIs (erlotinib or gefitinib). Improvements were seen in all prespecified subgroups, including patients with and without brain metastases.
In the FLAURA trial, the safety profile of osimertinib was consistent with previous experience. In patients treated with osimertinib, the most common adverse events (AEs) were diarrhea (58%, any grade [2% grade 3 or higher]) and dry skin (32%, any grade [less than 1% grade 3 or higher]), and in the comparator arm group the most common AEs were diarrhea (57%, any grade [2% grade 3 or higher]) and dermatitis acneiform (48%, any grade [5% grade 3 or higher]). Of the patients on osimertinib, 34% had a grade 3 or higher AE, compared to 45% in the comparator arm, and 13% of patients on osimertinib had an AE leading to treatment discontinuation compared to 18% in the comparator arm.
On September 28, 2017, the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) were updated to include the use of osimertinib in the first-line treatment of patients with locally advanced or metastatic EGFR mutation-positive NSCLC. The use of osimertinib for the first-line treatment of patients with locally-advanced or metastatic EGFR mutation-positive NSCLC is not yet FDA approved.
In the U.S., Tagrisso once-daily tablets are approved by the FDA for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after an EGFR TKI therapy. It is is the only approved medicine in the U.S. indicated for NSCLC patients who have tested positive for the EGFR T790M mutation.
The new breakthrough therapy designation acknowledges “the significant need for improved clinical outcomes in this disease,” said Sean Bohen, Executive Vice President of Global Medicines Development and Chief Medical Officer at AstraZeneca.
Source: AstraZeneca; October 9, 2017.