Tagrisso
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Overview

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

NCCN RECOMMENDED
PFSOS

Significantly improved progression-free survival1

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

PFSPFS

Consistent PFS improvement across all prespecified subgroups1

11 months longer mPFS in patients with CNS metastases (HR=0.47; 95% CI: 0.33, 0.66)

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; 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

  • PFS
  • PFS in subgroups
  • CNS response
  • Interim OS

TAGRISSO® plus chemotherapy significantly increased PFS1

PFS by blinded independent central review (BICR)†

PFS graphic 1

PFS BY INVESTIGATOR ANALYSIS*

PFS graphic 2
TAGRISSO® plus chemotherapy demonstrated consistent improvement
in median PFS across investigator and BICR analyses

Data cut-off: April 3, 2023.

† PFS by BICR was an additional sensitivity analysis.

* PFS by investigator analysis was the primary endpoint.

BICR: blinded independent central review; CI: confidence interval; HR: hazard ratio; NC: not calculable; PFS: progression free survival.

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 pemetrexed3
  • 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 permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.9.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed September 30, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  3. 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.
  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.

Professionals can request the mentioned references from AstraZeneca AG.