For the treatment of metastatic EGFRm NSCLC

First-line TAGRISSO nearly doubled median PFS1

Probability of PFS

Hazard ratio=0.46 (95% CI: 0.37, 0.57); N=556

PFS data PFS data

10.2 months

median PFS

(95% CI: 9.6, 11.1)

18.9 months

median PFS

(95% CI: 15.2, 21.4)

TAGRISSO P<0.0001

EGFR TKI Comparator

Months

  • In the FLAURA study, all US patients in the comparator arm received erlotinib2

Dr Jack West and colleagues discuss the FLAURA study

Interim Overall Survival (25% maturity)1,3

Overall Survival data were not mature at the time of the final PFS analysis1

Probability of Overall Survival

TAGRISSO Interim Overall Survival

TAGRISSO (n=279)

EGFR TKI Comparator (n=277)

Months

  • Overall Survival was a secondary endpoint in FLAURA

OVERALL SURVIVAL3

  TAGRISSO (n=279) EGFR TKI Comparator (n=277)
Percent alive at 6 months (95% CI) 98% (96-99) 93% (90-96)
Percent alive at 12 months (95% CI) 89% (85-92) 82% (77-86)
Percent alive at 18 months (95% CI) 83% (78-87) 71% (65-76)

First-line TAGRISSO delivered consistent PFS results across all patient types3

First-line TAGRISSO reduced the risk of progression or death across all prespecified subgroups,* including patients with or without CNS metastases3

TAGRISSO data across various subgroups TAGRISSO data across various subgroups

*Exploratory analysis.

All patient samples were EGFR positive by tissue biopsy.1,3

Adapted from: Soria et al. N Engl J Med. 2018.

NC, not calculable.

Dr Edward Kim and Dr Kathryn Mileham analyze the subgroup results in FLAURA

First-line TAGRISSO CNS data1,3,4

CNS overall response rate by BICR in patients with measurable CNS lesions at baseline1‡§

CNS OVERALL RESPONSE RATE

Confirmed Response Rate (%)

TAGRISSO vs EGFR TKI Comparator confirmed response rate TAGRISSO vs EGFR TKI Comparator confirmed response rate

77%

(95% CI: 55, 92)

18%

complete response

63%

(95% CI: 38, 84)

0%

complete response

TAGRISSO (n=22)

EGFR TKI Comparator (n=19)

CNS progression in the full study population irrespective of CNS lesion status at baseline3,4||

RATE OF CNS PROGRESSION

  TAGRISSO (n=279) EGFR TKI Comparator (n=277)
CNS metastases at study entry Known or treated (n=53) Not known or treated (n=226) Known or treated (n=63) Not known or treated (n=214)
Number of patients with CNS progression 10 (19%) 7 (3%) 27 (43%) 15 (7%)
Total CNS progression 17 (6%) 42 (15%)
  • This was a preplanned, exploratory analysis

According to RECIST v1.1.

§Based on confirmed response.

||Based on investigator assessment.

Progression events that do not occur within two scheduled visits of the last evaluable assessment, or randomization, are censored and therefore excluded in the number of events (excluding deaths).

BICR, blinded independent central review.

First-line TAGRISSO overall response rate and duration of response

Nearly 8 of 10 patients had a response on first-line TAGRISSO1

  • The overall response rate for TAGRISSO patients was 77% (95% CI: 71, 82) and 69% (95% CI: 63, 74) for patients on EGFR TKI comparator (erlotinib or gefitinib)1

Patients experienced a durable response on first-line TAGRISSO

  • The median duration of response for TAGRISSO patients was 17.6 months (95% CI: 13.8, 22.0) and 9.6 months (95% CI: 8.3, 11.1) for patients on EGFR TKI comparator (erlotinib or gefitinib)1

FLAURA: A phase 3, double-blind, randomized trial1-3

FLAURA Study Design for TAGRISSO FLAURA Study Design for TAGRISSO

Patients with metastatic NSCLC (N=556)

Key inclusion criteria

  • Stable, asymptomatic CNS metastases allowed
  • Exon 19 deletion/L858R (enrollment by local or central EGFR testing)
  • No prior systemic anti-cancer/EGFR TKI therapy

TAGRISSO (80 mg po qd) (n=279)

RANDOMIZED 1:1

EGFR TKI comparator# (n=277)

Erlotinib (150 mg po qd) (n=94)
or

Gefitinib (250 mg po qd) (n=183)

Crossover was allowed for patients in the EGFR TKI comparator arm upon confirmed progression and EGFR T790M positivity

Primary endpoint: PFS based on investigator assessment (according to RECIST v1.1)**

Secondary endpoints: Overall Survival, overall response rate, and duration of response

#Patients received either erlotinib or gefitinib as the sole comparator preselected by the trial site. All US patients in the comparator arm received erlotinib.2

**RECIST v1.1 assessment every 6 weeks (±1 week) until objective progressive disease. Every 12 weeks (±1 week) after 18 months.2

View full FLAURA study design on ClinicalTrials.gov

FLAURA BASELINE DEMOGRAPHICS1,3

Median age 64 years (range: 26-93)
Age <65 54%
Female 63%
Asian 62%
Never smokers 64%
WHO PS 0 or 1 100%
Visceral metastases†† 35%
CNS metastases‡‡ 21%

††Includes extrathoracic metastases.

‡‡Identified by CNS lesion site at baseline, medical history, and/or prior surgery, and/or prior radiotherapy to CNS metastases.

Osimertinib (TAGRISSO®) is the only National Comprehensive Cancer Network® (NCCN®) preferred first-line therapy option in metastatic EGFRm NSCLC. This preferred designation is based on efficacy, safety, and evidence.5§§

§§The NCCN Guidelines® do not endorse specific testing modalities or techniques for biomarker tests.

References: 1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018. 2. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125 [protocol]. 3. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. 4. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125 [supplementary appendix]. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V.3.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed February 4, 2019. 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.

Important Safety Information Expand

  • There are no contraindications for TAGRISSO

  • Interstitial lung disease (ILD)/pneumonitis occurred in 3.9% of the 1142 TAGRISSO-treated patients; 0.4% of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed

  • Heart rate-corrected QT (QTc) interval prolongation occurred in TAGRISSO-treated patients. Of the 1142 TAGRISSO-treated patients in clinical trials, 0.9% were found to have a QTc > 500 msec, and 3.6% of patients had an increase from baseline QTc > 60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia

  • Cardiomyopathy occurred in 2.6% of the 1142 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 3.9% of 908 patients who had baseline and at least one follow-up LVEF assessment. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO

  • Keratitis was reported in 0.7% of 1142 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist

  • Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose

  • Most common adverse reactions (≥20%) were diarrhea, rash, dry skin, nail toxicity, stomatitis, fatigue and decreased appetite

Indications

  • TAGRISSO is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

  • TAGRISSO is indicated for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy


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