osimertinib

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) used in the treatment of non-small cell lung cancer (NSCLC). It irreversibly inhibits signaling from mutant EGFR, including the T790M resistance mutation, while having greater selectivity for mutant receptors over wild-type EGFR, which can reduce some exposure-related side effects seen with earlier EGFR inhibitors. Osimertinib is marketed under the brand name Tagrisso and was developed by AstraZeneca.

Clinical use centers on tumors that harbor activating EGFR mutations. It is approved for patients with metastatic NSCLC whose tumors carry sensitizing EGFR mutations. It is also approved for T790M-positive disease after progression on prior EGFR inhibitors and, in several regulatory jurisdictions, as a first-line therapy for metastatic NSCLC with common activating mutations (such as exon 19 deletion or L858R) and for adjuvant therapy after complete resection of early-stage disease in EGFR-mutated cases.

Pharmacologically, osimertinib is taken orally, typically once daily. It has good central nervous system penetration and activity against brain metastases. It is metabolized mainly by CYP3A4 and is subject to drug interaction risk with strong CYP3A inhibitors or inducers, which may require dose adjustments.

Common adverse effects include diarrhea, dry skin, rash, nausea, decreased appetite, and fatigue. More serious but less frequent risks include interstitial lung disease or pneumonitis, cardiomyopathy with reduced ejection fraction, QT interval prolongation, and hepatotoxicity. Osimertinib is approved by multiple regulatory authorities worldwide and remains a standard option in the management of EGFR-mutated NSCLC.