First-line monotherapy: Adult patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.
First-line combination: With platinum-based chemotherapy for locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.
Stage III unresectable: Adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations.
Adjuvant: After tumor resection in adult patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.
Second-line: Adult patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, who have progressed on or after EGFR TKI therapy.
Monotherapy (all indications): 80 mg orally once daily, with or without food
In combination with chemotherapy: 80 mg orally once daily with pemetrexed 500 mg/m² and investigator's choice of cisplatin 75 mg/m² or carboplatin AUC 5 on Day 1 of 21-day cycles for 4 cycles, followed by osimertinib 80 mg daily plus pemetrexed maintenance every 3 weeks
Duration: Until disease progression or unacceptable toxicity (adjuvant: for 3 years or until recurrence/unacceptable toxicity)
Dose reduction: First reduction to 40 mg once daily. Discontinue if unable to tolerate 40 mg.
Strong CYP3A4 inducer coadministration: If unavoidable, increase to 160 mg once daily; resume 80 mg 3 weeks after discontinuation of the inducer
Tablets: 40 mg, 80 mg (film-coated)
None listed in the prescribing information.
Diarrhea (49%), Rash (45%), Musculoskeletal Pain (36%), Nail Toxicity (33%), Dry Skin (32%), Stomatitis (26%), Fatigue (22%), Neutropenia (20%)
Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.
Strong CYP3A4 Inducers: Avoid coadministration. If unavoidable, increase osimertinib dose to 160 mg daily.
Strong CYP3A4 Inhibitors: No clinically significant effect; no dose adjustment needed.
BCRP/P-gp Substrates: Osimertinib increases exposure of BCRP or P-gp substrates. Monitor for adverse reactions of concomitant BCRP or P-gp substrate drugs.
QTc Prolonging Drugs: Avoid concomitant use where feasible; if not, conduct periodic ECG monitoring.
Consult the full prescribing information for pregnancy-related considerations.
Refer to prescribing information for lactation guidance.
Pediatric safety and efficacy information is detailed in the full label.
Dose modifications for organ impairment are specified in the complete prescribing information.
Osimertinib is a third-generation, irreversible EGFR tyrosine kinase inhibitor that binds to certain mutant forms of EGFR (T790M, L858R, exon 19 deletion) at approximately 9-fold lower concentrations than wild-type EGFR. It also inhibits HER2, HER3, HER4, ACK1, and BLK at clinically relevant concentrations. Osimertinib distributes to the brain, with brain-to-plasma AUC ratios of approximately 2 in animal studies, supporting CNS activity.
Tmax: 6 hours (range 3–24). Bioavailability not determined for tablets. Vd: 918 L. Protein binding: 95%. Metabolized by CYP3A4/5 to active metabolites AZ5104 and AZ7550 (each ~10% of parent exposure). Half-life: ~48 hours. Elimination: feces 68%, urine 14%. Steady state by Day 15.
Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.
Tagrisso has FDA-approved indications across the following cancer types covered on PipelineEvidence: