Cited by 3,379Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentLung Cancer Research Studies

The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index; none of the 34 sources its claims cite is checked for support yet.

Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer

Open access

Abstract

BACKGROUND: Osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that is selective for both EGFR-TKI sensitizing and T790M resistance mutations in patients with non-small-cell lung cancer. The efficacy of osimertinib as compared with platinum-based therapy plus pemetrexed in such patients is unknown. METHODS: In this randomized, international, open-label, phase 3 trial, we assigned 419 patients with T790M-positive advanced non-small-cell lung cancer, who had disease progression after first-line EGFR-TKI therapy, in a 2:1 ratio to receive either oral osimertinib (at a dose of 80 mg once daily) or intravenous pemetrexed (500 mg per square meter of body-surface area) plus either carboplatin (target area under the curve, 5 [AUC5]) or cisplatin (75 mg per square meter) every 3 weeks for up to six cycles; maintenance pemetrexed was allowed. In all the patients, disease had progressed during receipt of first-line EGFR-TKI therapy. The primary end point was investigator-assessed progression-free survival. RESULTS: The median duration of progression-free survival was significantly longer with osimertinib than with platinum therapy plus pemetrexed (10.1 months vs. 4.4 months; hazard ratio; 0.30; 95% confidence interval [CI], 0.23 to 0.41; P<0.001). The objective response rate was significantly better with osimertinib (71%; 95% CI, 65 to 76) than with platinum therapy plus pemetrexed (31%; 95% CI, 24 to 40) (odds ratio for objective response, 5.39; 95% CI, 3.47 to 8.48; P<0.001). Among 144 patients with metastases to the central nervous system (CNS), the median duration of progression-free survival was longer among patients receiving osimertinib than among those receiving platinum therapy plus pemetrexed (8.5 months vs. 4.2 months; hazard ratio, 0.32; 95% CI, 0.21 to 0.49). The proportion of patients with adverse events of grade 3 or higher was lower with osimertinib (23%) than with platinum therapy plus pemetrexed (47%). CONCLUSIONS: Osimertinib had significantly greater efficacy than platinum therapy plus pemetrexed in patients with T790M-positive advanced non-small-cell lung cancer (including those with CNS metastases) in whom disease had progressed during first-line EGFR-TKI therapy. (Funded by AstraZeneca; AURA3 ClinicalTrials.gov number, NCT02151981 .).

Overview

Integrity signals

Registry

Crossref · 10.1056/nejmoa1612674

Cites

25 of 25 references verified0 citation errors · 0 not checkable

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Claims the paper makes

17 Own result · 13 Not checked yet · 8 Own method · 3 Own interpretation · 1 Sources not found · 1 Check pending

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  • It may state two separate claims as one. 12
  • Probably not a substantial claim. 7
17 of 17
  • The paper relies on this without support.

    Platinum-pemetrexed was the standard of care for patients with T790M-positive advanced NSCLC after first-line EGFR-TKI at the time of trial initiation.

    “Chemotherapy was the standard control at the time of trial initiation.”
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  1. Soria J, 2015, J Thorac Oncol, 10, S207

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Metadata

Authors
Mok, T. S., Wu, Y.-L., Ahn, M.-J., Garassino, M. C., Kim, H. R., Ramalingam, S. S., Shepherd, F. A., He, Y., Akamatsu, H., Theelen, W. S. M. E., Lee, C. K., Sebastian, M., Templeton, A., Mann, H., Marotti, M., Ghiorghiu, S., & Papadimitrakopoulou, V. A.
Affiliations
  • Army Medical University (CN)
  • Emory University (US)
  • Goethe University Frankfurt (DE)
  • AstraZeneca (United Kingdom) (GB)
  • The University of Texas MD Anderson Cancer Center (US)
Venue
New England Journal of Medicine
Published
2017-02-16
Volume
376
Issue
7
Pages
629-640
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
OpenAlex
W2560717039
Cited by
3,379
References
25
Citations by year
2026: 198 · 2025: 280 · 2024: 301 · 2023: 318 · 2022: 410 · 2021: 438 · 2020: 404 · 2019: 365 · 2018: 389 · 2017: 268
FWCI
305.08
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
  • Research Explorer (The University of Manchester) (submittedVersion, other-oa)
Funders
  • Cancer Research UK (20465)
  • National Cancer Institute (P30CA016672)
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, T790M mutation, non-small cell lung cancer, EGFR tyrosine kinase inhibitor resistance, pemetrexed, carboplatin, cisplatin, second-line therapy, progression-free survival, central nervous system metastasis, brain metastases, objective response rate, adverse events
MeSH terms
Pemetrexed, Acrylamides, Adult, Aged, Aged, 80 and over, Aniline Compounds, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Female, Humans, Indoles, Lung Neoplasms, Male, Middle Aged, Mutation, Piperazines, Platinum, Pyrimidines, Disease-Free Survival, Young Adult, ErbB Receptors

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