How Tagrisso Targets Lung Cancer
Tagrisso (osimertinib) treats non-small cell lung cancer (NSCLC), specifically tumors driven by EGFR mutations. It binds irreversibly to the EGFR protein on cancer cells, blocking signals that promote uncontrolled cell growth and tumor spread.[1]
Which Lung Cancers Does It Treat?
Tagrisso is approved for:
- First-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.
- Adjuvant therapy after tumor resection in early-stage (IB-IIIA) NSCLC with those same EGFR mutations.
- Treatment of metastatic NSCLC with T790M mutation after progression on prior EGFR therapies.[1][2]
It does not work for NSCLC without EGFR mutations or small cell lung cancer.
Mechanism of Action
EGFR is a receptor tyrosine kinase mutated in 10-15% of NSCLC cases, especially in non-smokers and Asians. These mutations cause the kinase to stay active, driving cancer proliferation, survival, and metastasis.
Tagrisso is a third-generation EGFR tyrosine kinase inhibitor (TKI). It:
- Fits into the ATP-binding site of mutant EGFR, including T790M-resistant forms.
- Forms a covalent bond, permanently disabling the kinase.
- Spares wild-type EGFR at therapeutic doses, reducing some side effects seen in first-generation TKIs like erlotinib.[1][3]
This leads to cancer cell death via apoptosis and inhibits tumor growth.
How It's Given and Treatment Duration
Patients take 80 mg orally once daily, with or without food. Treatment continues until disease progression or unacceptable toxicity. In adjuvant use, it's given for up to 3 years.[1][2]
Effectiveness from Clinical Trials
- FLAURA trial: Tagrisso doubled median progression-free survival (18.9 vs. 10.2 months) vs. first-generation TKIs in first-line metastatic EGFR-mutant NSCLC.[4]
- ADAURA trial: Reduced risk of recurrence or death by 83% in adjuvant setting.[2]
- Overall survival benefits shown in updated data, with 38-month median survival in first-line use.[3]
Real-world data confirm these results across diverse patients.
Common Side Effects and Risks
Frequent issues include diarrhea (58%), rash (58%), dry skin (36%), nail changes (35%), and fatigue. Serious risks: interstitial lung disease (3.4%), heart rhythm changes (QT prolongation), and embryo-fetal toxicity—contraindicated in pregnancy.[1]
Monitoring includes ECGs, lung imaging, and electrolyte checks.
How Tagrisso Compares to Other EGFR Inhibitors
| Drug | Generation | Key Strengths | Limitations |
|------|------------|---------------|-------------|
| Erlotinib (Tarceva), Gefitinib (Iressa) | 1st | First approved EGFR TKIs | Resistance via T790M mutation develops quickly |
| Afatinib (Gilotrif) | 2nd | Irreversible binder, broader mutations | More skin/ GI toxicity; no T790M activity |
| Tagrisso | 3rd | Overcomes T790M; brain penetration; better PFS/OS | Emerging C797S resistance |
Tagrisso outperforms earlier TKIs in progression-free and overall survival, especially with central nervous system metastases.[3][4]
Resistance and Next Steps After Progression
Resistance often arises from C797S mutation, MET amplification, or EGFR-independent pathways. Options include:
- Chemotherapy (platinum-pemetrexed).
- Combinations like amivantamab (for EGFR exon 20) or investigational trials.
- Liquid biopsy testing for new mutations.[3]
Who Makes Tagrisso and Access Issues
AstraZeneca manufactures Tagrisso. List price is about $17,000 per month in the US, but patient assistance programs and insurance often reduce costs.[5]
Patent Expiration: Key US patents expire in 2032-2034; generics unlikely before then. Check DrugPatentWatch.com for litigation updates.[6]
[1] Tagrisso Prescribing Information, AstraZeneca, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/208065s027lbl.pdf
[2] FDA Approval Summary, ADAURA Trial, 2021.
[3] NEJM: FLAURA Trial, 2018; updates 2022. https://www.nejm.org/doi/full/10.1056/NEJMoa1713137
[4] Lancet Oncology: Comparative Efficacy Review, 2020.
[5] GoodRx Pricing Data, 2023.
[6] DrugPatentWatch.com: Osimertinib Patents. https://www.drugpatentwatch.com/p/tradename/TAGRISSO