FDA Approves Osimertinib for First-Line Treatment of Metastatic NSCLC With Most Common EGFR Mutations


On April 18, the U.S. Food and Drug Administration (FDA) approved osimertinib (Tagrisso) 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 the multicenter, international, randomized, double-blind, active-controlled FLAURA trial 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 treatment of gefitinib (Iressa) 250 mg or erlotinib (Tarceva) 150 mg orally once daily. Of those randomized to standard of care, 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% confidence interval [CI] = 9.6–11.1) in the standard-of-care arm (hazard ratio = 0.46; 95% CI = 0.37–0.57), P < .0001). The confirmed overall response rate was 77% for the osimertinib arm and 69% for the standard-of-care arm. The estimated median response durations for the osimertinib and standard-of-care 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 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

Companion Diagnostic Test Approved

The FDA also granted a Premarket Approval (PMA) supplement for the cobas EGFR Mutation Test v2 to be used as a companion diagnostic test with osimertinib for first-line treatment of patients diagnosed with metastatic NSCLC whose tumors show EGFR exon 19 deletions or exon 21 L858R mutations. A companion diagnostic test is a medical device which provides information that is essential for the safe and effective use of a corresponding therapeutic product.

Clinical studies have demonstrated that patients diagnosed with NSCLC who test positive for defined mutations of the EGFR gene benefit from tyrosine kinase inhibitor therapies. The cobas EGFR Mutation Test v2 was previously FDA-approved as a companion diagnostic test with osimertinib for second-line treatment and beyond in NSCLC patients who test positive for the EGFR T790M mutation. The test is also a companion diagnostic test with erlotinib for patients with NSCLC who test positive for the EGFR exon 19 deletion or L858R-sensitizing mutations.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.