Osimertinib is an orally administered, mutant-selective EGFR tyrosine kinase inhibitor with activity against EGFR sensitizing mutations and T790M.
Pharmacokinetics
Current U.S. labeling reports an estimated mean plasma half-life of approximately 48 hours. Osimertinib is primarily metabolized through oxidation, predominantly involving CYP3A, and dealkylation. Two pharmacologically active metabolites, AZ7550 and AZ5104, have been identified.
Approximately 68% of elimination occurs through feces and 14% through urine, with unchanged osimertinib accounting for approximately 2% of elimination.
Molecular targets
Osimertinib inhibits mutant EGFR forms including:
- Exon 19 deletion
- Exon 21 L858R
- T790M
It also has activity against selected other EGFR alterations.
FLAURA
The FLAURA trial established osimertinib as an important first-line therapy for EGFR-mutated advanced NSCLC and demonstrated longer progression-free survival than first-generation EGFR TKIs.
ADAURA
ADAURA evaluated adjuvant osimertinib after complete tumor resection in EGFR-mutated stage IB–IIIA NSCLC. The trial showed a substantial disease-free survival benefit, with patients receiving osimertinib for three years.
FLAURA2
FLAURA2 evaluated first-line osimertinib with platinum-pemetrexed chemotherapy versus osimertinib alone. The trial demonstrated longer progression-free survival with combination therapy. Later overall-survival results showed median overall survival of 47.5 months versus 37.6 months, respectively.
LAURA
LAURA evaluated osimertinib after chemoradiation in unresectable stage III EGFR-mutated NSCLC. Median progression-free survival was 39.1 months with osimertinib versus 5.6 months with placebo.
Evidence limitations
Clinical-trial results describe populations meeting specific eligibility criteria and do not predict an individual patient’s response.