Cited by 3,190Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentLung Cancer Research Studies

The DOI matches its Crossref record; 15 of the 33 references it cites were found in a registry or an index, and 18 are not checked yet; none of the 17 sources its claims cite is checked for support yet.

First-Line Crizotinib versus Chemotherapy in ALK -Positive Lung Cancer

Open access

Abstract

BACKGROUND: The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown. METHODS: We conducted an open-label, phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease. Patients were randomly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy (pemetrexed, 500 mg per square meter of body-surface area, plus either cisplatin, 75 mg per square meter, or carboplatin, target area under the curve of 5 to 6 mg per milliliter per minute) every 3 weeks for up to six cycles. Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy. The primary end point was progression-free survival as assessed by independent radiologic review. RESULTS: Progression-free survival was significantly longer with crizotinib than with chemotherapy (median, 10.9 months vs. 7.0 months; hazard ratio for progression or death with crizotinib, 0.45; 95% confidence interval [CI], 0.35 to 0.60; P<0.001). Objective response rates were 74% and 45%, respectively (P<0.001). Median overall survival was not reached in either group (hazard ratio for death with crizotinib, 0.82; 95% CI, 0.54 to 1.26; P=0.36); the probability of 1-year survival was 84% with crizotinib and 79% with chemotherapy. The most common adverse events with crizotinib were vision disorders, diarrhea, nausea, and edema, and the most common events with chemotherapy were nausea, fatigue, vomiting, and decreased appetite. As compared with chemotherapy, crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life. CONCLUSIONS: Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. (Funded by Pfizer; PROFILE 1014 ClinicalTrials.gov number, NCT01154140.).

Checked 2026-10-06 · 18 references not checked yet

Overview

Integrity signals

Registry

Crossref · 10.1056/nejmoa1408440

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  • It may state two separate claims as one. 28
  • Probably not a substantial claim. 22
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  • The paper relies on this without support.

    The rank-preserving structural failure time model's assumptions are valid for estimating the effect of crizotinib after crossover adjustment.

    “As prespecified in the protocol, overall survival was also analyzed with the rank-preserving structural failure time model [20][21][22] to explore the effect of crossover to crizotinib in the chemotherapy group.”
    “After adjustment for crossover with the rank-preserving structural failure time model, the hazard ratio for death with crizotinib was 0.60 (95% CI, 0.27 to 1.42)”
  • The paper relies on this without support.

    Most advanced ALK-positive NSCLCs have nonsquamous histologic characteristics.

    “Given that most advanced ALK-positive NSCLCs have nonsquamous histologic characteristics, pemetrexed in combination with cisplatin or carboplatin was selected as the standard chemotherapy for this trial.”
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Metadata

Authors
Solomon, B. J., Mok, T., Kim, D.-W., Wu, Y.-L., Nakagawa, K., Mekhail, T., Felip, E., Cappuzzo, F., Paolini, J., Usari, T., Iyer, S., Reisman, A., Wilner, K. D., Tursi, J., & Blackhall, F.
Affiliations
  • Chinese University of Hong Kong (HK)
  • Seoul National University Hospital (KR)
  • Kindai University (JP)
  • Florida Hospital Cancer Institute (US)
  • Vall d'Hebron Hospital Universitari (ES)
  • Ospedale di Livorno (IT)
  • Pfizer (United States) (US)
  • University of Manchester (GB)
Venue
New England Journal of Medicine
Published
2014-12-04
Volume
371
Issue
23
Pages
2167-2177
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
OpenAlex
W2099530756
Cited by
3,190
References
33
Citations by year
2026: 92 · 2025: 142 · 2024: 185 · 2023: 220 · 2022: 256 · 2021: 296 · 2020: 302 · 2019: 363 · 2018: 365 · 2017: 375 · 2016: 347 · 2015: 233 · 2014: 10
FWCI
258.39
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • Digital Access to Libraries (submittedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
  • Open Repository and Bibliography (University of Liège) (submittedVersion, other-oa)
  • Research Explorer (The University of Manchester) (submittedVersion)
  • Seoul National University Open Repository (Seoul National University) (submittedVersion)
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
crizotinib, ALK-positive non-small cell lung cancer, anaplastic lymphoma kinase, ALK inhibitors, first-line therapy, progression-free survival, overall survival, objective response rate, quality of life, adverse events
MeSH terms
Pemetrexed, Crizotinib, Anaplastic Lymphoma Kinase, Adenocarcinoma, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Cisplatin, Female, Glutamates, Guanine, Humans, Lung Neoplasms, Male, Middle Aged, Pyrazoles, Pyridines, Carboplatin, Disease-Free Survival, Receptor Protein-Tyrosine Kinases, Protein Kinase Inhibitors, Kaplan-Meier Estimate

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