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Overview

ADJUVANT TAGRISSO® transforms the treatment options of resectable EGFRm NSCLC1

ESMO NCCN ASCO RECOMMENDED
OSDFS

Significantly improved overall survival1

-51 % reduced risk of death with ADJUVANT TAGRISSO® compared to the control arm in stage IB-IIIA
(HR=0.49 [95% CI: 0.34-0.70; P<0.0001])

DFSDFS

Lower risk of recurrence2

-73 % reduced risk of recurrence or death with ADJUVANT TAGRISSO® compared to the control arm in stage IB-IIIA (HR=0.27 [95% CI: 0.21-0.34])

CNSBrain

Fewer CNS recurrences and distant metastases2

-76 % reduced risk of brain metastases with ADJUVANT TAGRISSO® compared to the control arm in Stage II-IIIA (HR=0.24 [95% CI: 0.14-0.42])

-59 % reduction in the relative risk of distant metastases with ADJUVANT TAGRISSO® compared to the control arm (15% vs. 37%)

Watch in under 20 minutes a discussion on ADAURA's

  • 2022 DFS update and its significance for patients
  • relevance for Stage IB patients
  • benefits vs the fear of running out of treatment options
  • requirement of EGFRm testing

(click on a bullet point to start the video from this topic)

Download interview summary

Unmet need

Survival outcomes in resectable NSCLC10-12

Stage IB

Stadium IB

Stage II

Stadium II

Stage IIIA

Stadium III
Global 5-year overall survival* rates in patients with resectable NSCLC

Adjuvant chemotherapy has demonstrated an OS benefit of 5% vs no adjuvant chemotherapy10-12

*Median follow up for OS: 59.4 months; based on AJCC 7th edition staging10. Median follow up for OS: 86.4 months11; based on AJCC 8th edition staging.11,12
NSCLC: Non-small cell lung cancer

Question mark

What do you think? By what percentage does adjuvant chemotherapy alone lower the risk of death in patients with NSCLC after resection?

Across all stages, how high do you estimate the proportion of NSCLC patients with distant recurrence or CNS metastases after resection?

Question mark

Study design

ADAURA: global phase III study in patients with resectable EGFRm NSCLC (IB-IIIA)2

globale Phase-III-Studie bei Patienten mit reseziertem EGFRm NSCLC

Primary endpoint: Disease-free survival (DFS) in patients with NSCLC in stage II and IIIA (according to 7th AJCC edition*)

Secondary endpoints: DFS in the total population (stage IB-IIIA, according to 7th AJCC edition*), DFS after 2, 3, 4 and 5 years, overall survival, safety, health related quality of life.

  • * AJCC 7th edition: Stage IIIA includes stage IIIB patients (T3 N2 M0) according to the 8th edition.
  • † Centrally confirmed in tissue.
  • ‡ According to guidelines, at the discretion of the physician. Prior, subsequent or planned radiation was not permitted. Neoadjuvant chemotherapy was not permitted.
  • # Stratification factors: Stage (IB vs II vs IIIA), EGFRm (Ex19del vs L858R), ethnic ancestry (Asiatic vs non-Asiatic).
  • DFS: Disease-free survival; EGFR: Epidermal growth factor receptor; NSCLC: Non-small cell lung cancer.

Results

  • OS
  • OS in subgroups
  • DFS
  • DFS per stage
  • Recurrences

ADJUVANT TAGRISSO® significantly improves overall survival in stage IB-IIIA1

OS

Data cut-off: January 27, 2023
Data maturity was 18 % at the time of analysis (osimertinib 12%, placebo 24%); Median follow-up for OS: osimertinib 60.4 months, placebo 59.4 months.

Adapted according to Tsuboi M, et al. 20231
OS: Overall survival; HR: Hazard ratio.

Safety

Known safety and tolerability profile of TAGRISSO® in ADAURA2

Reported adverse events of all causes (≥10% of patients)

Berichtete unerwünschte Wirkungen aller Ursachen

Adapted according to Herbst R, et al. 20232

Data cut-off: April 11, 2022

  • Median duration of exposure: TAGRISSO® 35.8 months (range 0 to 38), placebo 25.1 months (range 0 to 39)
  • None of the adverse events that occurred in at least 10% of patients were grade 4 or higher
  • Adverse events that led to a dose reduction: TAGRISSO® n = 42 (12%); control arm n = 3 (1%)
  • Adverse events that led to treatment interruption: TAGRISSO® n = 91 (27%); control arm n = 43 (13%)
  • Adverse events that led to treatment discontinuation: TAGRISSO® n = 43 (13%); control arm n = 9 (3%)
  • Treatment related adverse events that led to death: TAGRISSO® n = 0; control arm n = 0
Treatment with ADJUVANT TAGRISSO® did not lead to a reduction in quality of life8

Unanswered questions

Find the answers to frequently asked questions here:

Why was ADJUVANT TAGRISSO® administered over 3 years in the ADAURA study?
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It is known from numerous analyses and studies in the adjuvant setting that the danger of recurrence is greatest within 2-3 years after tumour resection.1,2 Correspondingly, 45% of all EGFRm patients in the control arm had a recurrence after two years (despite adjuvant chemotherapy in about 60% of patients).3 Based on prior experiences, the investigators together with AstraZeneca had appraised a treatment duration of three years to be appropriate for the ADAURA study.

References:

  • Kelly K, et al. Adjuvant Erlotinib Versus Placebo in Patients With Stage IB-IIIA Non-Small-Cell Lung Cancer (RADIANT): A Randomized, Double-Blind, Phase III Trial. J Clin Oncol.2015;33(34):4007-4014.
  • Pennell NA, et al. SELECT: A Phase II Trial of Adjuvant Erlotinib in Patients With Resected Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer. J Clin Oncol.2018;37(2):97-104.
  • Herbst R, et al. Adjuvant Osimertinib for resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer: Updated results from the phase III randomized ADAURA trial. J Clin Oncol 2023.
At what timepoint after resection should the treatment with ADJUVANT TAGRISSO® be started?
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In the ADAURA study, patients began the TAGRISSO therapy1

  • up to 10 weeks after surgery if they received no adjuvant chemotherapy in order to allow recovery following the surgery.
  • up to 26 weeks after surgery if they received an adjuvant therapy to allow completion of a maximum of 4 cycles of chemotherapy, recovery from it, and recovery from surgery.

References:

  • Wu Y-L, et al. ADAURA investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020; 383(18): 1711-1723.
Do the results of the ADAURA study indicate that an EGFR mutation test should be performed for all lung cancer patients in the early stages?
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The EGFR mutation test is recommended for NSCLC patients independent of stage by various guidelines (ESMO, NCCN and ASCO).1-3

The compelling efficacy proven in the ADAURA study of ADJUVANT TAGRISSO® changed the treatment options for resected EGFRm NSCLC (Ex19del or L858R mutation) and further elevated the utility of molecular testing.4

The ASCO guidelines additionally advise against immunotherapy with atezolizumab in EGFR mutated early stage NSCLC patients.3 In order to be able to make this therapy decision, it is important to know the EGFR mutation status in all NSCLC patients.

References:

  • Remon J, Soria JC, Peters S, on behalf of the ESMO Guidelines Committee, 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, https://doi.org/10.1016/j.annonc.2021.08.1994 Annals of Oncology 2021; 32(12): 1637-42.
  • Referenziert mit der Genehmigung von 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 gibt keinerlei Garantien in Bezug auf deren Inhalt oder Verwendung und lehnt jegliche Verantwortung für deren Verwendung in irgendeiner Weise ab.
  • Pisters, K., et al. “Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage I-IIIA Completely Resected Non–Small-Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update.” 0(0): JCO 2022, DOI https://doi.org/10.1200/JCO.22.00051.
  • Wu Y-L, et al. ADAURA investigators. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020; 383(18): 1711-1723.
More information about FIRST-LINE TAGRISSO® (FLAURA)

References:

  1. Tsuboi M, et al., Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. N Engl J Med. 2023. 389:137–47. doi: 10.1056/NEJMoa2304594.
  2. Herbst R, et al. Adjuvant Osimertinib for resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer: Updated results from the phase III randomized ADAURA trial. J Clin Oncol 2023.
  3. 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; 32(12): 1637-42.
  4. 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.
  5. Pignon J, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE collaborative group. J Clin Oncol. 2008;26(21):3552–3559.
  6. Tsuboi M, et al. Osimertinib adjuvant therapy in patients with resected EGFR mutated NSCLC (ADAURA): CNS disease recurrence. Presented at: 2020 ESMO Virtual Congress; September 19, 2020.
  7. Peters S, et al. The impact of brain metastasis on quality of life, resource utilization and survival in patients with non-small-cell lung cancer. Can Treat Rev. 2016;45:139–162.
  8. Majem M, et al. Patient reported outcomes from ADAURA: Osimertinib as adjuvant therapy in patients with resected EGFR mutated (EGFRm) NSCLC. Presented at: 2020 WCLC Virtual Congress; January 29, 2021.
  9. Pisters K, et al. Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage I-IIIA Completely Resected Non–Small-Cell Lung Cancer: ASCO Guideline Rapid Recommendation Update. J Clin Oncol 2022; 40:1127-1130.
  10. Peters S, et al. Lungscape: Resected NSCLC outcome by clinical and pathological parameters. JTO 2014; 9: 1675-1684.
  11. Aokage et al. Clinical pathological staging validation in the eighth edition of the TNM classification for lung cancer: Correlation between solid size on thin-section computed tomography and invasive size in pathological findings in the new T classification. JTO 2017; 12:1403-1412.
  12. Goldstraw P, et al. The IASLC Lung Cancer Staging Project: The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer, JTO 2016; 11:39-51.

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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