On February 16, 2024, osimertinib (Tagrisso) was approved by the U.S. Food and Drug Administraton (FDA) with pemetrexed and platinum-based chemotherapy for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with tumors having EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test, and no prior systemic therapy for advanced disease.1
Supporting Efficacy Data
Approval was based on the open-label phase III FLAURA2 trial (ClinicalTrials.gov identifier NCT04035486). In this trial, 557 patients were randomly assigned to receive osimertinib plus pemetrexed and platinum-based chemotherapy (n = 279) or osimertinib alone (n = 278).
Investigator-assessed median progression-free survival was 25.5 months (95% confidence interval [CI] = 24.7 months to not estimable) in the osimertinib-plus-chemotherapy group vs 16.7 months (95% CI = 14.1–21.3 months) in the osimertinib-alone group (hazard ratio = 0.62, 95% CI = 0.49–0.79, P < .0001).
How It Is Used
The recommended osimertinib dose is 80 mg once daily until disease progression or unacceptable toxicity. Product labeling provides instructions on dosage modification for adverse reactions. Concomitant use with strong CYP3A inducers (eg, glucocorticoids, rifampin, phenobarbital) should be avoided.
Safety Profile
In FLAURA2, the most common adverse events of any grade in the osimertinib-plus-chemotherapy group were rash (49% vs 41% in the osimertinib-alone group), diarrhea (43% vs 41%), stomatitis (31% vs 21%), nail toxicity (27% vs 32%), and dry skin (24% vs 31%). The most common grade 3 or 4 laboratory abnormalities were neutropenia (36%), leukopenia (20%), thrombocytopenia (16%), and lymphopenia (16%).
OF NOTE
Osimertinib has warnings/precautions for interstitial lung disease/pneumonitis; QTc interval prolongation; cardiomyopathy; keratitis; erythema multiforme major, Stevens-Johnson syndrome, and toxic epidermal necrolysis; cutaneous vasculitis; aplastic anemia; and embryofetal toxicity.
Osimertinib has warnings/precautions for interstitial lung disease/pneumonitis; QTc interval prolongation; cardiomyopathy; keratitis; erythema multiforme major, Stevens-Johnson syndrome, and toxic epidermal necrolysis; cutaneous vasculitis; aplastic anemia; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving osimertinib.
REFERENCE
1. Tagrisso (osimertinib) tablets, for oral use, prescribing information, AstraZeneca. Available at https://www.tagrissohcp.com. Accessed February 27, 2024.
