FDA has approved Tagrisso (osimertinib) for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.
The drug is sponsored by AstraZeneca Pharmaceuticals LP.
Approval was based on a multicenter, international, randomized, double-blind, active-controlled trial (FLAURA, NCT02296125) conducted in 556 patients with EGFR exon 19 deletion or exon 21 L858R mutation-positive, unresectable or metastatic NSCLC who had not received previous systemic treatment for advanced disease.
The trial results were presented at the European Society of Medical Oncology 2017 Congress and published in the New England Journal of Medicine.
Patients were randomized (1:1) to receive osimertinib 80 mg orally once daily or “standard-of-care” treatment of gefitinib 250 mg or erlotinib 150 mg orally once daily. Of those randomized to SOC, 20% received osimertinib as the next line of antineoplastic therapy.
The estimated median progression-free survival was 18.9 months (95% CI: 15.2, 21.4) in the osimertinib arm and 10.2 months (95% CI: 9.6, 11.1) in the SOC arm (hazard ratio 0.46 (95% CI: 0.37, 0.57), p<0.0001). The confirmed overall response rate was 77% for the osimertinib arm and 69% for the SOC arm. The estimated median response durations for the osimertinib and SOC arms were 17.6 and 9.6 months, respectively. At the time of the primary PFS analysis, there were too few deaths to estimate or compare survival outcomes.
The recommended dose of osimertinib is 80mg orally once daily, with or without food.
In the US, Tagrisso is already approved for the 2nd-line treatment of patients with metastatic EGFRm NSCLC, whose disease has progressed on or after a 1st-line EGFR-TKI therapy and who have developed the secondary T790M mutation, as detected by an FDA-approved test.
In 2017, Tagrisso was granted Breakthrough Therapy and Priority Review designations by the FDA in the first-line treatment setting. Tagrisso is under regulatory review in the European Union and Japan for use in the 1st-line treatment setting with regulatory decisions anticipated in the second half of 2018.
Full prescribing information is available here.