Uses

Osimertinib is a third-generation EGFR kinase inhibitor indicated as adjuvant therapy following tumor resection in adults with NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations, for locally advanced unresectable stage III NSCLC after chemoradiation, and for metastatic EGFR-mutant NSCLC including T790M-positive disease after prior EGFR inhibitor therapy.

Do not use if

No absolute contraindications are listed in the FDA label. Caution in patients with QTc prolongation risk factors or left ventricular dysfunction.

Side effects

Common adverse effects include diarrhea, rash, dry skin, nail toxicity, stomatitis, and fatigue. Serious risks include interstitial lung disease/pneumonitis, QTc interval prolongation, cardiomyopathy, keratitis, and erythema multiforme/Stevens-Johnson syndrome.

Warnings

Monitor for pulmonary symptoms suggestive of ILD/pneumonitis and permanently discontinue if confirmed. Obtain ECG in patients at risk of QTc prolongation. Assess LVEF before and during treatment. Use effective contraception; drug is embryo-fetal toxic.

How it works

Osimertinib irreversibly binds to and inhibits mutant EGFR forms (T790M, L858R, exon 19 deletions) with approximately 9-fold selectivity over wild-type EGFR, thereby blocking tumor cell proliferation and survival signaling. It has two active circulating metabolites (AZ7550, AZ5104).

Storage

Store at room temperature between 20–25°C (68–77°F). Keep in original container away from moisture.