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Cited by 2,914Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentLung Cancer Research Studies

Overall Survival with Osimertinib in Untreated, EGFR -Mutated Advanced NSCLC

Open access
Ramalingam, Suresh S., Vansteenkiste, Johan, Planchard, David, Cho, Byoung Chul, Gray, Jhanelle E., Ohe, Yuichiro, Zhou, Caicun, Reungwetwattana, Thanyanan +16 more·2020·New England Journal of Medicine
DOI 10.1056/nejmoa1913662
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Abstract

BACKGROUNDOsimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKIsensitizing and EGFR T790M resistance mutations.A phase 3 trial compared firstline osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC).The trial showed longer progressionfree survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46).Data from the final analysis of overall survival have not been reported. METHODSIn this trial, we randomly assigned 556 patients with previously untreated advanced NSCLC with an EGFR mutation (exon 19 deletion or L858R allele) in a 1:1 ratio to receive either osimertinib (80 mg once daily) or one of two other EGFR-TKIs (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily, with patients receiving these drugs combined in a single comparator group).Overall survival was a secondary end point. RESULTSThe median overall survival was 38.6 months (95% confidence interval [CI], 34.5 to 41.8) in the osimertinib group and 31.8 months (95% CI, 26.6 to 36.0) in the comparator group (hazard ratio for death, 0.80; 95.05% CI, 0.64 to 1.00; P = 0.046).At 3 years, 79 of 279 patients (28%) in the osimertinib group and 26 of 277 (9%) in the comparator group were continuing to receive a trial regimen; the median exposure was 20.7 months and 11.5 months, respectively.Adverse events of grade 3 or higher were reported in 42% of the patients in the osimertinib group and in 47% of those in the comparator group. CONCLUSIONSAmong patients with previously untreated advanced NSCLC with an EGFR mutation, those who received osimertinib had longer overall survival than those who received a comparator EGFR-TKI.The safety profile for osimertinib was similar to that of the comparator EGFR-TKIs, despite a longer duration of exposure in the osimertinib group.(Funded by AstraZeneca; FLAURA ClinicalTrials.govnumber, NCT02296125.

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Crossref · 10.1056/nejmoa1913662

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  • The second- and third-generation TKIs have shown significantly longer PFS compared with first-generation TKIs, and osimertinib has shown superior OS compared with first-generation TKIs.

    “The second- and third-generation TKIs have shown significantly longer PFS compared with first-generation TKIs, and the third-generation TKI, osimertinib, has shown superior OS compared with first-generation TKIs.”

    From Afatinib for the treatment of <i>EGFR</i> mutation-positive NSCLC: A review of clinical findings (2020) · cites this paper as [49]

    The Abstract reports significantly longer progression-free survival with third-generation osimertinib than with gefitinib or erlotinib, and longer overall survival; the Discussion also states the overall-survival benefit. The paper does not establish the claimed progression-free-survival advantage for second-generation TKIs over first-generation TKIs. Page numbers are not available in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In the FLAURA trial, first-line osimertinib led to superior PFS and OS compared with a first-generation TKI (gefitinib or erlotinib).

    “in the recent FLAURA head-to-head trial, first-line treatment with osimertinib led to superior PFS and OS compared with a first-generation TKI (gefitinib or erlotinib).”

    From Afatinib for the treatment of <i>EGFR</i> mutation-positive NSCLC: A review of clinical findings (2020) · cites this paper as [49]

  • Patients with classical EGFR mutations show marked improvements in clinical outcomes when treated with first-, second- or third-generation tyrosine kinase inhibitors (TKIs).

    “Patients with classical EGFR mutations (L858R or exon 19 deletions (Ex19del)) show marked improvements in clinical outcomes when treated with first-, second- or third-generation tyrosine kinase inhibitors (TKIs)4–6,11.”

    From Structure-based classification predicts drug response in EGFR-mutant NSCLC (2021) · cites this paper as [11]

  • In the first line setting, EGFR-TKIs have shown efficacy, particularly with osimertinib.

    “In the first line setting, EGFR-tyrosine kinase inhibitors have shown efficacy, particularly with osimertinib. 21 22”

    From Sacituzumab tirumotecan versus docetaxel for previously treated <i>EGFR</i> -mutated advanced non-small cell lung cancer: multicentre, open label, randomised controlled trial (2025) · cites this paper as [22]

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Research works printed but not linked: 1

  1. Wu YL, Ahn MJ, Garassino MC, et al. CNS efficacy of osimertinib in patients The New England Journal of Medicine . For personal use only. No other uses without permission. Copyright © 2020 Massachusetts Medical Society. All rights reserved. n engl j med 382;

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Authors
Ramalingam, S. S., Vansteenkiste, J., Planchard, D., Cho, B. C., Gray, J. E., Ohe, Y., Zhou, C., Reungwetwattana, T., Cheng, Y., Chewaskulyong, B., Shah, R., Cobo, M., Lee, K. H., Cheema, P., Tiseo, M., John, T., Lin, M.-C., Imamura, F., Kurata, T., Todd, A., Hodge, R., Saggese, M., Rukazenkov, Y., & Soria, J.-C.
Affiliations
  • Université Paris-Sud (FR)
  • From Winship Cancer Institute, Emory University School of Medicine, Atlanta (S.S.R.); the Respiratory Oncology Unit, Department of Respiratory Medicine, University Hospital KU Leuven, Leuven, Belgium (J.V.); the Thoracic Unit, Department of Medical Oncology, Institut Gustave Roussy, Villejuif (D.P., J.-C.S.), and University Paris Sud, Orsay (J.-C.S.) — both in France; the Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul...
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2020-01-02
Volume
382
Issue
1
Pages
41-50
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1913662
OpenAlex
W2990041408
Cited by
2,914
References
27
Citations by year
2026: 354 · 2025: 462 · 2024: 487 · 2023: 411 · 2022: 480 · 2021: 434 · 2020: 284 · 2019: 1
FWCI
222.81
Type
journal article
Language
en
Open access
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
  • Lirias (submittedVersion)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
AstraZeneca (N/A)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords
osimertinib, EGFR-mutant non-small cell lung cancer, EGFR tyrosine kinase inhibitors, gefitinib, erlotinib, first-line therapy, overall survival, exon 19 deletion, L858R mutation, T790M resistance, progression-free survival, adverse events, treatment duration
MeSH terms
Erlotinib Hydrochloride, Gefitinib, Acrylamides, Aged, Aniline Compounds, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Double-Blind Method, Female, Humans, Indoles, Lung Neoplasms, Male, Middle Aged, Mutation, Pyrimidines, Proportional Hazards Models, Protein Kinase Inhibitors, Kaplan-Meier Estimate, ErbB Receptors

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