Tagrisso
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Overview

TAGRISSO® plus chemotherapy for improved efficacy in patients with poor prognosis1#

NCCN RECOMMENDED
PFSPFS

Significantly improved progression-free survival1

9 months longer mPFS vs TAGRISSO® alone (HR=0.62; 95% CI: 0.48, 0.80)

OSOS

Significant overall survival benefit3

4 years median OS, 9.9 months longer mOS vs TAGRISSO® alone (HR=0.77; 95% CI: 0.61, 0.96)

CNSZNS

Higher CNS responses4

48 % complete responses in the CNS vs 16% with TAGRISSO® alone

# TAGRISSO® plus chemotherapy approved for patients with EGFRm (ex19del, L858R) non-squamous NSCLC.
CI: confidence interval; CNS: central nervous system; HR: hazard ratio; mPFS: median progression-free survival; NCCN: National Comprehensive Cancer Network; OS: overall survival; PFS: progression free survival.

Study design

FLAURA-2 investigated the efficacy of TAGRISSO® plus chemotherapy in the first-line setting1

Flaura-2 study design

Modular treatment intensification: patients who received TAGRISSO® plus chemotherapy could discontinue or modify chemotherapy and continue on TAGRISSO®1

Primary endpoint: PFS based on investigator assessment, additional sensitivity analysis per BICR assessment

Key secondary endpoints: Overall survival, objective response rate, duration and depth of response, disease control rate, and PFS2 and safety

Prespecified exploratory endpoint: Efficacy in patients with CNS metastases at baseline4

Brain scans were performed at screening and at the time of progression in all patients

* 6 patients who were randomised did not receive treatment.1

AUC: area under the curve; BICR: blinded independent central review; CNS: central nervous system; ECOG: Eastern Cooperative Oncology Group; EGFR: epidermal growth factor receptor; EGFRm: epidermal growth factor receptor mutation; mNSCLC: metastatic non-small cell lung cancer; NSCLC: non-small cell lung cancer; PFS: progression-free survival; PFS2: secondary progression-free survival, defined as time from randomisation until disease progression or death on the second line of therapy following the study treatment; PS: performance status; q3w: every 3 weeks; TKI: tyrosine kinase inhibitor.

Results

  • OS
  • PFS
  • Poor prognostic factors
  • CNS response

TAGRISSO® plus chemotherapy significantly increased OS3

graphic
At 3-year landmark, 63% of patients in the TAGRISSO® + chemotherapy
arm were alive, a 12% improvement over monotherapy.

OS maturity: 57%. Median OS follow-up was 51.2 months (range: 0.2, 60.4) for TAGRISSO® + chemotherapy vs 51.3 months (0.1, 60.1) for TAGRISSO®

CI: confidence interval; HR: hazard ratio; NC: not calculated; OS: overall survival.

Chemotherapy was the most common first subsequent treatment5

chemotherapy graph

Patient disposition

  • Received second-line therapy
  • No subsequent treatment
  • Still on study treatment
  • Did not receive study treatment
    (TAGRISSO® + CTx, n=2; TAGRISSO®,n=4)

Second-line therapies

  • Other*
  • TAGRISSO® + targeted agent /
    investigational drug (no chemotherapy)
  • EGFR-TKI (other than TAGRISSO®),
    monotherapy or combination
  • Platinum-based chemotherapy
  • Non-platinum-based chemotherapy

* “Other” includes monotherapy immunotherapy, antibody drug conjugates, targeted agents or investigational drugs not otherwise specified.

Data cut-off April 3, 2023

CTx: chemotherapy; EGFR: epidermal growth factor receptor; TKI: tyrosine kinase inhibitor.

Safety

Safety results from the FLAURA-2 study1

  • Adverse events
  • AE incidence over time
Adverse events table

ILD was reported in 3% of patients in the combination arm and 4% in the monotherapy arm (all grades)

In the TAGRISSO® plus chemotherapy arm:

  • At data cutoff, 56% of patients were still receiving TAGRISSO® and 25% of patients were still receiving pemetrexed in the combination arm1
  • Patients received median total exposure of 22.3 months for TAGRISSO® and 8.3 months for pemetrexed7
  • 11% of patients discontinued TAGRISSO® due to an adverse event, 25% due to progression, and 5% due to other reasons1
  • 76% of patients completed 4 cycles of platinum-based chemotherapy; the median number of pemetrexed cycles given was 124
  • Among the 75% of patients who discontinued pemetrexed: 43% did so due to adverse events, 11% due to progression, 11% due to patient decision, and 10% due to other reasons1
Adverse events seen were consistent with the established profiles of
the individual agents; no new safety signals were identified1

* One patient experienced grade 5 COVID-19 in the TAGRISSO® with the addition of chemotherapy arm.

Data cut-off: April 3, 2023.

ALT: alanine transaminase; AST: aspartate aminotransferase; COVID-19: coronavirus disease 2019; ILD: interstitial lung disease.

More information about FIRST-LINE TAGRISSO® (FLAURA)

References:

  1. Planchard D, Jänne PA, Cheng Y, et al. FLAURA2 Investigators. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948 [including supplementary appendix].
  2. Referenced with the approval of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V.8.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Access on 24/09/2025. 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. Planchard D, et al. First-line osimertinib + chemotherapy versus osimertinib monotherapy in EGFRm advanced NSCLC: FLAURA2 final overall survival. Presented at: IASLC 2025 World Conference on Lung Cancer, September 6-9, 2025; Barcelona, Spain.
  4. Jänne PA, Planchard D, Kobayashi K, et al. CNS efficacy of osimertinib with or without chemotherapy in epidermal growth factor receptor-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2023 Dec 2:JCO2302219.
  5. Valdiviezo N, Okamoto I, Hughes BGM, et al. First-line osimertinib ± platinum-pemetrexed in EGFRm advanced NSCLC: FLAURA2 post-progression outcomes [oral presentation]. Presented at: ELCC; March 20-23, 2024; Prague, Czech Republic.
  6. Jänne PA, et al. FLAURA2: exploratory overall survival analyses in patients with poorer prognostic factors treated with osimertinib ± platinum–pemetrexed as first-line treatment for EGFR-mutated advanced NSCLC. Presented at: ESMO Congress 2025; October 17-21, 2025; Berlin, Germany.
  7. Planchard D, Jänne PA, Cheng Y, et al. FLAURA2: safety and CNS outcomes of first-line osimertinib ± chemotherapy in EGFRm advanced NSCLC [oral presentation]. Presented at: ESMO Congress; October 20-24, 2023; Madrid, Spain.

Professionals can request the mentioned references from AstraZeneca AG.