Tagrisso
Request personal visitSign up for the AZ E-Information Service
Share

Overview

FIRST-LINE TAGRISSO® – THE STANDARD FOR THE FIRST-LINE THERAPY OF ADVANCED EGFRm NSCLC1,2#

ESMO NCCN PREFERRED
OSOS

Longer survival

38,6 months – first and only EGFR TKI with >3 years statistically significant OS3

  • vs 31.8 months OS for gefitinib/erlotinib (HR = 0.799; p = 0.0462)
PFSPFS

Later progression

18,9 months – a PFS that has never been achieved before4*

  • vs 10.2 months PFS for gefitinib/erlotinib (HR = 0.46; p < 0.0001)
CNSZNS

Less CNS progression

52 % significant reduction in the risk of CNS progression3,5

  • vs gefitinib/erlotinib (HR = 0.48; p = 0.014)
  • # Based on the ESMO and NCCN Guidelines. Osimertinib (TAGRISSO®) is the only first-line monotherapy option for patients with advanced EGFRm NSCLC preferred by the European Society for Medical Oncology (ESMO) Guidelines Committee and National Comprehensive Cancer Network® (NCCN®).
  • * Based on monotherapies in the 1L.

Study design

FIRST-LINE therapy for advanced NSCLC with EGFR mutation4

FIRST-LINE TAGRISSO® was studied in a double-blind, randomised phase III study vs EGFR TKI comparator arm (gefitinib/erlotinib)4

Primary endpoint: PFS determined by the investigator (RECIST v1.1)4

Secondary endpoint: OS, ORR, DoR, DCR, depth of response, safety4

  • * Patients with asymptomatic or stable CNS metastases were included; symptomatic/ non-stable CNS metastases were allowed if they were stable for ≥2 weeks after stopping the definitive therapy and taking corticosteroids.4
    Tumour assessments were performed at baseline and then every 6 weeks for 18 months. Subsequently, the assessment took place every 12 weeks until disease progression. Brain imaging at baseline was prescribed only for patients with known or suspected brain metastases, with follow-up imaging in patients with confirmed CNS metastases.4
  • # 47%: 85/180 patients, who have received a second-line therapy. 31%: 85/277 patients of the EGFR TKI comparator arm.
  • OS: Overall survival; ORR: Objective response rate; DoR: Median duration of response; DCR: Disease control rate.

Results

  • OS
  • PFS
  • CNS progression
  • Patients under therapy

FIRST-LINE TAGRISSO® provides a statistically significant benefit over sequential therapy with TAGRISSO® 2L3

STATISTICALLY SIGNIFICANT OVERALL SURVIVAL (OS)

Statistisch signifikantes Gesamtüberleben (os)
Despite 47% Crossover, significantly longer survival with FIRST-LINE TAGRISSO®3
  • Adapted according to Ramalingam et al. 2019.3
  • # 47%: 85/180 patients, who have received a second-line therapy. 31%: 85/277 patients of the EGFR TKI comparator arm.
Question mark

Do you use TAGRISSO® in patients with metastatic EGFRm NSCLC for first-line therapy or do you prefer its use in a later therapy line?

Safety

Preferable tolerability profile of TAGRISSO® despite almost double the exposure time3

FIRST-LINE TAGRISSO - bessere Verträglichkeit vs. Vergleichsarm
  • *Grouped term.
  • **Listed are adverse events that occurred in at least 10% of patients in both study arms. The safety analyses included all patients who had received at least one dose of an investigational preparation (safety analysis set). Some patients had more than one adverse event. In the osimertinib group, the only adverse events were 4th grade stomatitis and renal symptoms (1 patient each); the only 5th grade adverse event was renal symptoms (1 patient). In the comparator arm, the only grade 4 adverse event was an elevation in alanine aminotransferase level (4 patients); the only grade 5 undesirable event was diarrhoea (1 patient). In the comparator arm, 1 patient had diarrhoea of unknown grade and 1 patient had nausea of unknown grade. #The most frequent undesirable events in the kidneys in both experimental groups were an increase in creatinine levels in the blood, one acute renal damage, one proteinuria, dysuria and haematuria.
  • ADR: adverse drug reaction; fewer ADR grade ≥3 for osimertinib 42% vs 47% in comparator arm; ALT: alanine aminotransferase; AST: aspartate aminotransferase; EKG: electrocardiogram.

Unanswered questions

Find the answers to frequently asked questions here:

To what extent does the use of first-line TAGRISSO® therapy differ from the use of other approved EGFR TKIs?
+

As first-line therapy, treatment with Tagrisso® improves progression-free survival significantly and leads to a prolongation of overall survival never achieved before compared to other EGFR TKIs.1-4

TAGRISSO® can pass the blood-brain barrier much better5, is effective against existing brain metastases and reduces the occurrence of new brain metastases.6 Furthermore, therapy with TAGRISSO® is better tolerated compared to other EGFR TKIs.1,3,4

The ESMO and NCCN Guidelines recommend TAGRISSO® as the preferred treatment for first-line therapy.7,8

References:

  • Soria JC et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer; N Engl J Med 2018; 378(2) inkl. Appendix: 113–125. 6.
  • Ramalingam SS, et al. Overall Survival with Osimertinib in Untreated, EGFR-Mutated advanced NSCLC; N Engl J Med. 2020; 382:41-50.
  • Wu, Y.L., et al., Dacomitinib versus gefitinib as first-line treatment for patients with EGFR mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol, 2017. 18(11): p. 1454-1466.
  • Park, K., et al., Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomized controlled trial. Lancet Oncol, 2016. 17(5): p. 577-89.
  • Ballard P et al. Preclinical comparison of osimertinib with other EGFR-TKIs in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res. 2016;22(20):5130–5140.
  • Reungwetwattana T et al. CNS Response to Osimertinib Versus Standard Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients With Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 36:3290-3297.
  • Planchard, D., et al., Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2018. 29(Suppl 4): p. iv192-iv237, Updated version published 15 September 2020 by the ESMO Guidelines Committee, https://www.esmo.org/guidelines/lung-and-chest-tumours/clinical-practice-living-guidelines-metastatic-non-small-cell-lung-cancer.
  • Referenced with the approval of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V.1.2023. ©National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Access on 1/12/2023. NCCN gives no guarantee of any kind with regard to their content or use and rejects any responsibility for their use in any way.
Why is it so important to know the EGFR mutation status before starting treatment?
+

Clinical studies indicate that EGFR- or ALK-positive tumours rarely respond adequately to immunotherapy treatments.1

Given the lower clinical benefit, current treatment guidelines do not recommend IO treatment for EGFR- or ALK-positive tumours.2,3

For this reason, the ESMO Expert Board recommends the simultaneous testing of PD-L1 status and molecular testing for EGFR to ensure that an appropriate therapy can be started.1

References:

  • Passaro A, Leighl N, Blackhall F, Popat S, Kerr K, Ahn MJ, Arcila ME, Arrieta O, Planchard D, de Marinis F, Dingemans AM, Dziadziuszko R, Faivre-Finn C, Feldman J, Felip E, Curigliano G, Herbst R, Jänne PA, John T, Mitsudomi T, Mok T, Normanno N, Paz-Ares L, Ramalingam S, Sequist L, Vansteenkiste J, Wistuba II, Wolf J, Wu YL, Yang SR, Yang JCH, Yatabe Y, Pentheroudakis G, Peters S, ESMO expert consensus statements on the management of EGFR mutant Non-Small Cell Lung Cancer, Annals of Oncology (2022), doi: https://doi.org/10.1016/j.annonc.2022.02.003.
  • Planchard, D., et al., Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2018. 29 (Suppl 4): p. iv192-iv237. Updated version published 15 September 2020 by the ESMO Guidelines Committee, https://www.esmo.org/guidelines/lung-and-chest-tumours/clinical-practice-living-guidelines-metastatic-non-small-cell-lung-cancer.
  • Referenced with the approval of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V.1.2023. ©National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Access on 1/12/2023. NCCN gives no guarantee of any kind with regard to their content or use and rejects any responsibility for their use in any way.
More information about FIRST-LINE TAGRISSO® + chemotherapy (FLAURA-2)

References:

  1. Planchard D, et al; on behalf of the ESMO Guidelines Committee. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Originally published in 2018 – Ann Oncol. 2018:29(Suppl 4):iv192–iv237.Updated version published 15 September 2020 by the ESMO Guidelines Committee, https://www.esmo.org/guidelines/lung-and-chest-tumours/clinical-practice-living-guidelines-metastatic-non-small-cell-lung-cancer.
  2. Referenced with the approval of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V.1.2023. ©National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Access on 1/12/2023. NCCN gives no guarantee of any kind with regard to their content or use and rejects any responsibility for their use in any way.
  3. Ramalingam SS, et al. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC; N Engl J Med. 2020; 382:41-50.
  4. Soria JC, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer; N Engl J Med 2018; 378(2) inkl. Appendix: 113–125.
  5. Reungwetwattana T, et al. CNS Response to Osimertinib Versus Standard Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients With Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2018 36:3290-3297.

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.

×