April 19, 2018—Yesterday evening, the U.S. Food and Drug Administration (FDA) approved the use of osimertinib, a third-generation EGFR inhibitor, for the first-line treatment of patients with metastatic EGFR-positive non-small cell lung cancer (NSCLC). Osimertinib is specifically approved for patients whose tumors harbor exon 19 deletions or exon 21 L858R mutations in EGFR.
 
As a third-generation, irreversible EGFR tyrosine kinase inhibitor, osimertinib is designed to inhibit both EGFR-sensitizing and EGFR T790M-resistance mutations. Osimertinib has demonstrated clinical activity against CNS metastases.
 
This approval follows the results of the phase III FLAURA trial (NCT02296125) in which 556 patients were randomized to receive osimertinib (n=279) or standard EGFR-directed therapies, erlotinib or gefitinib (n=277). The use of frontline osimertinib reduced the risk of progression or death by 54% compared with other EGFR inhibitors. In the trial, median progression-free survival (PFS) was 18.9 months (95% CI, 15.2-21.4) for patients receiving osimertinib compared with 10.2 months (95% CI, 9.6-11.1) for patients receiving standard therapy.
 
The objective response rate for osimertinib was 77% compared with 69% for erlotinib or gefitinib. Further, the median duration of response with osimertinib was estimated to be 17.6 months compared with 9.6 months for patients receiving standard therapy. Median overall survival had not yet been reached for either treatment arm.
 
The most common adverse events (AEs) for patients treated with osimertinib included diarrhea, rash, dry skin, nail toxicity, stomatitis, and decreased appetite. Serious AEs were reported in 4% of patients receiving osimertinib and included pneumonia, pneumonitis, and pulmonary embolism.
 
Osimertinib was initially approved in November 2015 for patients with EGFR T790M-mutated NSCLC following progression on or after another EGFR inhibitor. Yesterday’s announcement expands that indication to the first-line.
 
Full prescribing information for osimertinib is available here.
 
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Jonathan A. Bell
Published Online: Thursday, April 19, 2018