Mechanism of action
TAGRISSO®: Developed for the effective and selective inhibition of EGFR sensitising and resistance mutations.1,2
TAGRISSO® is an irreversible third generation EGFR TKI developed:1,2
- For inhibition of EGFR sensitising mutations (exon 19 deletions and exon 21 L858R point mutation).1,2*
- For inhibition of the occurrence of EGFR T790M resistance mutation.2,3
- With minimal activity against wild-type EGFR1*
Inhibits effectively† both sensitising EGFRm as well as EGFR T790M1-3*
Minimal activity against wild-type EGFR1*
* As proven in preclinical in-vitro studies.
† Refers to the efficacy to inhibit at the receptor level.
Dosage
Dosing and administration of TAGRISSO®1
Oral administration
80 mg once daily.*
Administration independent of mealtimes:
Administration should take place at the same time every day.
Water soluble:
suitable for drinking and feeding tube accessible.*
* Instructions for use
- A dose adjustment based on patient age, body weight, gender, ethnic group or smoking status is not required. If a dose reduction is necessary, the dose of TAGRISSO® should be lowered to 40 mg once per day.
- The concomitant use of St. John’s wort is contraindicated; it should be stopped 3 weeks before starting TAGRISSO®.
- If the patient is not capable of swallowing the film-coated tablet, it can be dissolved first in 50 ml of non-carbonated water. Add the film-coated tablet whole to the water (do not crush), stir until it disintegrates and take immediately. Refill the glass halfway in order to be sure that no residue remains and drink immediately. No other liquids may be used.
- If administration must take place via a nasogastral tube, follow the same procedure as above. However, the quantity of water in this case is 15 ml for the initial dissolving and 15 ml for the rinsing. The resulting 30 ml of liquid are to be administered according to the instruction manual for the nasogastral tube with corresponding water rinses. The administration of the dispersion and the drug residue should take place within 30 minutes after the film-coated tablet was put into water.
Dose adjustments
Depending on individual safety and tolerability, treatment interruptions and/or dose reductions may be required.1
Guideline Recommendations
- ESMO Guidelines
- NCCN Guidelines
Turquoise: general categories or stratification; light turquoise: systemic anticancer therapy; light green: combination of treatments or other systemic treatments; white: other aspects of management.
cfDNA, cell-free DNA; ChT, chemotherapy; EGFR, epidermal growth factor receptor; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of Molecular Targets; FDA, Food and Drug Administration; MCBS, ESMO-Magnitude of Clinical Benefit Scale; mNSCLC, metastatic non-small-cell lung cancer; NGS, nextgeneration sequencing; PS, performance status; RT, radiotherapy; TKI, tyrosine kinase inhibitor.
aESMO-MCBS v1.1111 was used to calculate scores for new therapies/indications approved by the EMA or FDA. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms).
bPreferred option.
cESCAT scores apply to alterations from genomic-driven analyses only. These scores have been defined by the guideline authors and validated by the ESMO Translational Research and Precision Medicine Working Group.4 See Supplementary Table S1, available at https://doi.org/10.1016/j.annonc.2022.12.009 for more information on ESCAT scores.
dRecommended treatment option for patients with a major uncommon, non-exon 20 insertion, sensitising EGFR mutation [III, B; ESMO-MCBS v1.1 score: 4 for afatinib; ESCAT: I-B].
eESMO-MCBS v1.1 score for the combination of bevacizumab with gefitinib or erlotinib.
fNot EMA approved.
gPatients who have moderate radiological progression with ongoing clinical benefit may continue with EGFR TKIs [III, A].
References:
- TAGRISSO® Information for Healthcare Professionals, www.swissmedicinfo.ch
- Cross DAE, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4(9):1046-1061.
- Ramalingam SS, et al. Osimertinib as first-line treatment of EGFR mutation–positive advanced non–small-cell lung cancer. J Clin Oncol. 2018;36(9):841-849.
- Varrone A, et al. A PET study in healthy subjects of brain exposure of 11C-labelled osimertinib – a drug intended for treatment of brain metastases in non-small cell lung cancer. J Cereb Blood Flow Metab. 2020;40(4):799-807.
- Referenced with the approval of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V5.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Access on 05/14/2024. NCCN gives no guarantee of any kind with regard to their content or use and rejects any responsibility for their use in any way.
- Remon J. et al. Early and locally advanced non-small-cell lung cancer: an update of the ESMO Clinical Practice Guidelines focusing on diagnosis, staging, systemic and local therapy, Annals of Oncology (2021), doi: https://doi.org/10.1016/j.annonc.2021.08.1994.
- Hendriks LE. et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up; Ann Oncol. 2023;34(4):339-357.
TAGRISSO®
Comp: Osimertinib; 40 mg and 80 mg film-coated tablets; List A. Ind: TAGRISSO is indicated as monotherapy for the adjuvant treatment after complete tumour resection in adult patients with non-squamous, non-small cell lung cancer (NSCLC) with EGFR (epidermal growth factor receptor) exon 19 deletions or exon 21 (L858R) substitution mutations, for the first-line treatment in adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR‑T790M‑mutation who have progressed on or after EGFR TKI therapy, as well as in combination with pemetrexed and platinum‑based chemotherapy for the first-line treatment of adult patients with locally advanced or metastatic, non-squamous NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations. Dos: 80 mg once daily in monotherapy as well as in combination with pemetrexed and 4 cycles platinum-based chemotherapy. CI: Hypersensitivity to the active substance or to any of the excipients. Concomitant use of St. John’s Wort. W&P: Interstitial lung disease. Erythema multiforme. QTc interval prolongation. LVEF and cardiomyopathy. Diarrhoea. Age and body weight. IA: Strong CYP3A inducers. CYP3A4 substrates and transporters. ADRs: Very common: diarrhoea, stomatitis, rash, dry skin, paronychia, pruritus, platelet count decreased, leukocytes decreased, lymphocytes decreased, neutrophils decreased, blood creatinine increased. Common: interstitial lung disease, epistaxis, palmar-plantar erythrodysaesthesia syndrome, alopecia, urticaria, blood creatine phosphokinase increased, QTc interval prolongation, cardiac failure, left ventricular ejection fraction decreased, erythema multiforme, skin hyperpigmentation. Uncommon, rare, very rare: see www.swissmedicinfo.ch. Date of revision of the text: December 2023.
Further information: www.swissmedicinfo.ch or AstraZeneca AG, Neuhofstrasse 34, 6340 Baar, Switzerland. www.astrazeneca.ch.
Professionals can request the mentioned references from AstraZeneca AG.
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