On April 18, 2018, the Food and Drug Administration approved osimertinib (Tagrisso, AstraZeneca Pharmaceuticals LP) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.
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. Patients were randomized (1:1) to receive osimertinib 80 mg orally once daily or “standard-of-care (SOC)” 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 (PFS) 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), p0.0001).>
The most common adverse reactions (occurring in at least 20% of patients treated with osimertinib) were diarrhea, rash, dry skin, nail toxicity, stomatitis, and decreased appetite. Serious adverse reactions were reported in 4% of patients treated with osimertinib. The most common serious adverse reactions (≥1%) were pneumonia (2.9%), ILD/pneumonitis (2.1%), and pulmonary embolism (1.8%).
The recommended dose of osimertinib is 80 mg orally once daily, with or without food.
Full prescribing information is available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208065s008lbl.pdf.
FDA granted this application Priority review and Breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).
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