Mechanism of action for Tagrisso (osimertinib)

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Mechanism of Action

TAGRISSO is a tyrosine kinase inhibitor, or a TKI.^1,2

TAGRISSO selectively targets EGFR sensitising mutations (ex19del and L858R) and the T790M acquired resistance mutation.^1–3 TAGRISSO crosses the intact BBB, as seen in a PET study of healthy human volunteers (n=7) and EGFRm NSCLC patients with brain metastases (n=4).*^1,2

Image of a cancer cell with an EGFR receptor on and a TAGRISSO labelled for mode of action

*PET images following administration of microdoses of [¹¹C] osimertinib in EGFRm NSCLC patients with brain metastases (n=4) and healthy volunteers (n=7) demonstrated that the brain to plasma ratio (Kp) was similar and that [¹¹C] osimertinib crossed the BBB rapidly and was homogeneously distributed across all regions of the brain in both patients and healthy volunteers.^1,2

BBB, blood-brain barrier; EGFR, epidermal growth factor receptor; EGFRm, EGFR mutation; NSCLC, non-small cell lung cancer; PET, positron emission tomography; TKI, tyrosine kinase inhibitor

For advanced NSCLC, TAGRISSO with platinum-pemetrexed chemotherapy brings together two familiar treatment modalities to address tumour heterogeneity, particularly in those eligible patients at higher risk of progression, like those with CNS metastases, L858R mutation, extensive disease and those suitable for a more intensive approach.^1,2,4,5

Image of a cancer cell with an EGFR receptor on and TAGRISSO and chemotherapy labelled for mode of action

*PET images following adminstration of microdoses of [¹¹C]osimertinib in EGFRm NSCLC patients with brain metastases (n=4) and healthy volunteers (n=7) demonstrated that the brain to plasma ratio (Kp) was similar and that [¹¹C]osimertinib crossed the BBB rapidly and was homogeneously distributed across all regions of the brain in both patients and healthy volunteers^.1,2

BBB, blood-brain barrier; CNS, central nervous system; DNA, deoxyribonucleic acid; EGFR, epidermal growth factor receptor; EGFRm, EGFR mutation; NSCLC, non-small cell lung cancer

The FLAURA2 trial included the use of two platinum-based chemotherapy protocols – both cisplatin and carboplatin – allowing choice in patient and treatment management.⁶

Treat tumour cells with cytotoxic chemotherapy:

Platinum-based chemotherapy triggers cytotoxic processes that lead to cell death⁵
Pemetrexed disrupts metabolic processes essential for cell replication⁷
Studies shows that the BBB may be disrupted in the presence of brain metastases, which allows chemotherapy agents to cross more easily^8,9

Explore TAGRISSO’s results

ADAURA

Adjuvant after complete tumour resection Stage IB - IIIA EGFRm NSCLC 

Explore ADAURA

FLAURA

Advanced metastatic (Stage IV) EGFRm NSCLC 

Explore FLAURA

FLAURA2

Advanced metastatic (Stage IV) EGFRm NSCLC, TAGRISSO with platinum pemetrexed chemotherapy

Explore FLAURA2

LAURA

Unresectable Stage III EGFRm NSCLC  

Explore LAURA

BBB, blood-brain barrier; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutant; ex19del, exon 19 deletion; Kp, brain to plasma ratio; L858R, exon 21 substitution; NSCLC, non-small cell lung cancer; PET, positron emission tomography; TKI, tyrosine kinase inhibitor; T790M, exon 20 threonine 790 methionine substitution

*based on NHS initiations as per Blueteq, December 2024.

TAGRISSO (osimertinib) 40 mg Summary of Product Characteristics.
TAGRISSO (osimertinib) 80 mg Summary of Product Characteristics.
Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61.
Lim ZF, Ma PC. Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy. J Hematol Oncol. 2019 Dec 9;12(1):134.
Zhang C, Xu C, Gao X, Yao Q. Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics. 2022;12(5):2115-32.
Planchard D, Jänne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, et al. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023 Nov 23;389(21):1935-48.
Adjei AA. Pharmacology and mechanism of action of pemetrexed. Clin Lung Cancer. 2004 Apr;5 Suppl 2:S51-5.
Ye LY, Sun LX, Zhong XH, Chen XS, Hu S, Xu RR, et al. The structure of blood-tumor barrier and distribution of chemotherapeutic drugs in non-small cell lung cancer brain metastases. Cancer Cell Int. 2021 Oct 24;21(1):556.
Zimmermann S, Dziadziuszko R, Peters S. Indications and limitations of chemotherapy and targeted agents in non-small cell lung cancer brain metastases. Cancer Treat Rev. 2014 Jul;40(6):716-22.
Su PL, et al. Survival benefit of osimertinib combination therapy in patients with T790M-positive non-small-cell lung cancer refractory to osimertinib treatment. Lung Cancer. 2021;158: 137-145.

GB-63997 | DOP: July 2025

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Mechanism of Action

TAGRISSO is a tyrosine kinase inhibitor, or a TKI.1,2

TAGRISSO selectively targets EGFR sensitising mutations (ex19del and L858R) and the T790M acquired resistance mutation.1–3 TAGRISSO crosses the intact BBB, as seen in a PET study of healthy human volunteers (n=7) and EGFRm NSCLC patients with brain metastases (n=4).*1,2

The FLAURA2 trial included the use of two platinum-based chemotherapy protocols – both cisplatin and carboplatin – allowing choice in patient and treatment management.6

TAGRISSO with chemotherapy may synergistically amplify antitumour effects (based on preclinical in-vitro models).6,10

Explore TAGRISSO’s results

Abbreviations and References

TAGRISSO is a tyrosine kinase inhibitor, or a TKI.^1,2

TAGRISSO selectively targets EGFR sensitising mutations (ex19del and L858R) and the T790M acquired resistance mutation.^1–3 TAGRISSO crosses the intact BBB, as seen in a PET study of healthy human volunteers (n=7) and EGFRm NSCLC patients with brain metastases (n=4).*^1,2

The FLAURA2 trial included the use of two platinum-based chemotherapy protocols – both cisplatin and carboplatin – allowing choice in patient and treatment management.⁶

TAGRISSO with chemotherapy may synergistically amplify antitumour effects (based on preclinical in-vitro models).^6,10