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.

Learn more about the mechanism of action of TAGRISSO®

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 V2.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Access on 02/21/2024. NCCN gives no guarantee of any kind with regard to their content or use and rejects any responsibility for their use in any way.
  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.

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.