Osimertinib (Tagrisso)
General information
Class/mechanism: Mutant-selective EGFR tyrosine kinase inhibitor. Osimertinib preferentially binds irreversibly to certain mutant forms of the epidermal growth factor receptor (EGFR) (T790M, L858R, and exon 19 deletion) at approximately 9-times lower concentrations than wild-type. Two pharmacologically-active metabolites of osimertinib, AZ7550 and AZ5104, also emerge at about 10% the level of osimertinib. AZ7550 had similar potency to osimertinib. AZ5104 had about 8-times greater potency against exon 19 deletion and T790M mutants than osimertinib and 15-times greater potency against wild-type EGFR. Osimertinib also inhibits activity of HER2, HER3, HER4, ACK1, and BLK.[1][2][3]
Route: PO
Extravasation: n/a
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]
Resistance mechanisms
- 2019: Leonetti et al. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer
Diseases for which it is used
Patient drug information
- Osimertinib (Tagrisso) package insert[1]
- Osimertinib (Tagrisso) patient drug information (Chemocare)[4]
- Osimertinib (Tagrisso) patient drug information (UpToDate)[5]
History of changes in FDA indication
- 11/13/2015: FDA granted accelerated approval "for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy."[1]
- 3/30/2017: FDA granted regular approval "for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy."[1]
- 4/18/2018: FDA approved "for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test."
Also known as
- Code name: AZD9291
- Brand name: Tagrisso