Osimertinib

Overview

Osimertinib, sold under the brand name Tagrisso, is a medication used to treat non-small-cell lung carcinomas with specific mutations. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor.[1][2][3] WP

The most common side effects include diarrhea, rash, musculoskeletal pain, dry skin, skin inflammation around nails, sore mouth, fatigue, and cough.[4] WP

Osimertinib was approved for medical use in the United States in November 2015, and in the European Union in February 2016.[5][6] WP

Uses, dosage and effects

Medical uses

Osimertinib is used to treat locally advanced or metastatic non-small-cell lung cancer (NSCLC), if the cancer cells are positive for the T790M or L858R mutation (or certain deletion mutations) in the gene coding for EGFR or for activating EGFR mutations.^, The T790M mutation may be de novo or acquired following first-line treatment with other EGFR tyrosine kinase inhibitors, such as gefitinib, erlotinib, and afatinib.[7][8][9] WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.

In the US, EGFR exon 19 deletions, exon 21 L858R mutations, or the T790M status of the patient must be detected by a companion diagnostic test before treatment with osimertinib. The Food and Drug Administration (FDA) has approved multiple tests, including FoundationOne CDx for this purpose. In Europe and elsewhere, activating EGFR mutations or T790M mutations may be determined by a validated test.[7][10][11] WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.

In February 2024, the FDA approved osimertinib, in combination with platinum-based chemotherapy, for people with locally advanced or metastatic non-small cell lung cancer whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.[12] WP

In September 2024, the FDA approved osimertinib for adults with locally advanced, unresectable (stage III) non-small cell lung cancer (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, as detected by an FDA-approved test.[13] WP

Development of resistance

In people treated with osimertinib, resistance usually develops within approximately ten months. Resistance mediated by an exon 20 C797S mutation accounts for the majority of resistance cases, which has resulted in multiple attempts with non-ATP competitive or allosteric inhibitors to try and offset this acquired resistance by targeting other regions of the RTK kinase domain.[14][15][16] WP

Risks and side effects

Adverse effects

Very common (greater than 10% of clinical trial subjects) adverse effects include diarrhea, stomatitis, rashes, dry or itchy skin, infections where finger or toenails abut skin, low platelet counts, low leukocyte counts, and low neutrophil counts.[17] WP

Common (between 1% and 10% of clinical trial subjects) adverse effects include interstitial lung disease.[17] WP

It can cause fetal harm.[7][18] WP

Interactions

Interactions

Osimertinib is metabolized by CYP3A4 and CYP3A5, so substances that strongly inhibit either enzyme, like macrolide antibiotics, antifungals, and antivirals may increase exposure to osimertinib, and substances like rifampicin that activate either enzyme may decrease the effectiveness of osimertinib.[7][17] WP

Pharmacology

Pharmacology

Osimertinib preferentially binds irreversibly to mutated epidermal growth factor receptor proteins, particularly those with more common mutations in lung cancer such as L858R mutation or an exon 19 deletion.[7] WP

It exhibits linear pharmacokinetics; the median time to Cmax is 6 hours (range 3–24 hours). The estimated mean half-life is 48 hours, and oral clearance (CL/F) is 14.3 (L/h). 68% of elimination is by feces and 14% by urine.[7] WP

History

History

The drug discovery program that led to osimertinib started in 2009 and yielded the drug by 2012; the process was structure-driven and aimed to find a third-generation EGFR inhibitor that would selectively target the T790M form of the EGFR receptor.[19] WP

Osimertinib was designated as a breakthrough therapy in April 2014, based on phase I trial results, and the drug was provisionally approved under the FDA accelerated approval program with a priority review voucher, in November 2015.[5][19][20] WP

In February 2016, the EMA provisionally approved osimertinib under an accelerated process—the first approval under the program.[6][19] WP

In February 2024, the FDA approved osimertinib, in combination with platinum-based chemotherapy, for people with locally advanced or metastatic non-small cell lung cancer whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. Efficacy was evaluated in FLAURA 2 (NCT04035486), an open-label, randomized trial of 557 participants with EGFR exon 19 deletion or exon 21 L858R mutation-positive la/mNSCLC and no prior systemic therapy for advanced disease. Participants were randomized 1:1 to receive either osimertinib with platinum-based chemotherapy or osimertinib monotherapy. The application was granted priority review, fast track, breakthrough therapy, and orphan drug designations.[12] WP

Legal status

Economics

At launch, in the United States, AstraZeneca priced the drug at US$12,750 per month.[21] WP

Chemistry

Formula

C28H33N7O2 PC

CAS number

1421373-65-0 PC

Molar mass (g/mol)

499.6 PC

IUPAC name (computed by PubChem)

N-[2-[2-(dimethylamino)ethyl-methylamino]-4-methoxy-5-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]phenyl]prop-2-enamide PC

SMILES

CN1C=C(C2=CC=CC=C21)C3=NC(=NC=C3)NC4=C(C=C(C(=C4)NC(=O)C=C)N(C)CCN(C)C)OC PC

InChIKey

DUYJMQONPNNFPI-UHFFFAOYSA-N PC

PubChem CID

71496458

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Marshall, Helen. Tagrisso (osimertinib). 26 January 2022
2. Journal / agency Remon J, Steuer CE, Ramalingam SS. Osimertinib and other third-generation EGFR TKI in EGFR-mutant NSCLC patients. Annals of Oncology. January 2018. doi:10.1093/annonc/mdx704
3. Journal / agency Tan CS, Gilligan D, Pacey S. Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer. The Lancet Oncology. September 2015. doi:10.1016/S1470-2045(15)00246-6 · PMID 26370354
4. Journal / agency FDA Approves First Adjuvant Therapy for Most Common Type of Lung Cancer. 18 December 2020
5. Journal / agency New Drug Application (NDA): 208065. 22 December 2015
6. Journal / agency Tagrisso EPAR. 23 June 2026
7. Journal / agency Tagrisso- osimertinib tablet, film coated. 25 September 2024
8. Journal / agency Gijtenbeek RG, Damhuis RA, van der Wekken AJ, Hendriks LE, Groen HJ, van Geffen WH. Overall survival in advanced epidermal growth factor receptor mutated non-small cell lung cancer using different tyrosine kinase inhibitors in The Netherlands: a retrospective, nationwide registry study. The Lancet Regional Health - Europe. April 2023. doi:10.1016/j.lanepe.2023.100592 · PMID 36817181 · PMC9932646
9. Journal / agency Xu M, Xie Y, Ni S, Liu H. The latest therapeutic strategies after resistance to first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in patients with non-small cell lung cancer (NSCLC). Annals of Translational Medicine. May 2015. doi:10.3978/j.issn.2305-5839.2015.03.60 · PMID 26015938 · PMC4430733
10. Journal / agency List of FDA-Authorized Companion Diagnostic Devices (In Vitro and Imaging Tools). 23 July 2026
11. Journal / agency Tagrisso: EPAR - Product Information. 23 June 2026
12. Journal / agency FDA approves osimertinib with chemotherapy for EGFR-mutated non-small cell lung cancer. 20 February 2024
13. Journal / agency FDA approves osimertinib for locally advanced, unresectable (stage III) non-small cell lung cancer following chemoradiation therapy. 25 September 2024
14. Journal / agency Patel H, Pawara R, Ansari A, Surana S. Recent updates on third generation EGFR inhibitors and emergence of fourth generation EGFR inhibitors to combat C797S resistance. European Journal of Medicinal Chemistry. December 2017. doi:10.1016/j.ejmech.2017.05.027 · PMID 28526474
15. Journal / agency Wang S, Song Y, Liu D. EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance. Cancer Letters. January 2017. doi:10.1016/j.canlet.2016.11.008 · PMID 27840244
16. Journal / agency Saraon P, Pathmanathan S, Snider J, Lyakisheva A, Wong V, Stagljar I. Receptor tyrosine kinases and cancer: oncogenic mechanisms and therapeutic approaches. Oncogene. 2 June 2021. doi:10.1038/s41388-021-01841-2 · PMID 34079087
17. Other UK label. 26 January 2017
18. Journal / agency Bollinger MK, Agnew AS, Mascara GP. Osimertinib: A third-generation tyrosine kinase inhibitor for treatment of epidermal growth factor receptor-mutated non-small cell lung cancer with the acquired Thr790Met mutation. Journal of Oncology Pharmacy Practice. July 2018. doi:10.1177/1078155217712401 · PMID 28565936
19. Journal / agency Yver A. Osimertinib (AZD9291)-a science-driven, collaborative approach to rapid drug design and development. Annals of Oncology. June 2016. doi:10.1093/annonc/mdw129 · PMID 26961148
20. Journal / agency Approved Drugs - Osimertinib. 13 November 2015
21. Other AHRQ Healthcare Horizon Scanning System – Potential High-Impact Interventions Report Priority Area 02: Cancer. December 2015

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.