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Cited by 3,381Lung Cancer Treatments and MutationsLung Cancer Research StudiesLung Cancer Diagnosis and Treatment

Crizotinib versus Chemotherapy in Advanced ALK -Positive Lung Cancer

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Shaw, Alice T., Kim, Dong-Wan, Nakagawa, Kazuhiko, Seto, Takashi, Crinó, Lucio, Ahn, Myung-Ju, De Pas, Tommaso, Besse, Benjamin +15 more·2013·New England Journal of Medicine
DOI 10.1056/nejmoa1214886
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Abstract

BACKGROUND: In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. METHODS: We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival. RESULTS: The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy. CONCLUSIONS: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.).

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  • Previously reported serious potential adverse events with crizotinib were hepatotoxic and pulmonary toxic effects.

    “More serious potential adverse events previously reported with crizotinib were hepatotoxic and pulmonary toxic effects.10”

    From First-Line Crizotinib versus Chemotherapy in <i>ALK</i> -Positive Lung Cancer (2014) · cites this paper as [10]

  • In a randomized phase 3 trial in previously treated advanced ALK-positive NSCLC, crizotinib was more effective than single-agent second-line pemetrexed or docetaxel.

    “In a randomized phase 3 trial involving patients with advanced ALK-positive NSCLC who had received previous platinum-based chemotherapy, crizotinib showed efficacy superior to that of single-agent second-line chemotherapy with either pemetrexed or docetaxel.10”

    From First-Line Crizotinib versus Chemotherapy in <i>ALK</i> -Positive Lung Cancer (2014) · cites this paper as [10]

  • In PROFILE 1007, median PFS was 7.7 months with crizotinib versus 3.0 months with chemotherapy (HR 0.49, 95% CI 0.37-0.64, P<0.001).

    “The median PFS, as determined by independent radiological review, was 7.7 months (95% CI: 6.0-8.8) in the crizotinib group, compared with 3.0 months (95% CI: 2.6-4.3) in the chemotherapy group (HR for disease progression or death with crizotinib 0.49, 95% CI: 0.37-0.64,P < 0.001).”

    From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [135]

  • In that second-line trial, PFS was 7.7 months (95% CI, 6.0 to 8.8) with crizotinib compared with 3.0 months (95% CI, 2.6 to 4.3) with chemotherapy (HR, 0.49; 95% CI, 0.37 to 0.64; P < .001).

    “The PFS results were 7.7 months (95% CI, 6.0 to 8.8) with crizotinib compared with 3.0 months (95% CI, 2.6 to 4.3) with chemotherapy (HR, 0.49; 95% CI, 0.37 to 0.64; P < .001).”

    From Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update (2015) · cites this paper as [56]

  • In an interim analysis of the second-line trial comparing crizotinib with chemotherapy, median OS was 20.3 months (95% CI, 18.1 to not reached) for crizotinib versus 22.8 months (95% CI, 18.6 to not reached) for chemotherapy (HR, 1.02; 95% CI, 0.68 to 1.54; P = .54).

    “An interim analysis found a median OS of 20.3 months (95% CI, 18.1 to not reached) for crizotinib versus 22.8 months (95% CI, 18.6 to not reached) for chemotherapy (HR, 1.02; 95% CI, 0.68 to 1.54; P = .54).”

    From Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update (2015) · cites this paper as [56]

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Authors
Shaw, A. T., Kim, D.-W., Nakagawa, K., Seto, T., Crinó, L., Ahn, M.-J., De Pas, T., Besse, B., Solomon, B. J., Blackhall, F., Wu, Y.-L., Thomas, M., O'Byrne, K. J., Moro-Sibilot, D., Camidge, D. R., Mok, T., Hirsh, V., Riely, G. J., Iyer, S., Tassell, V., Polli, A., Wilner, K. D., & Jänne, P. A.
Affiliations
  • Massachusetts General Hospital (US)
  • Seoul National University Hospital (KR)
  • Kindai University (JP)
  • National Hospital Organization Kyushu Cancer Center (JP)
  • Samsung Medical Center (KR)
  • Institut Gustave Roussy (FR)
  • Peter MacCallum Cancer Centre (AU)
  • The Christie NHS Foundation Trust (GB)
  • Guangdong General Hospital (CN)
  • Cancer Trials Ireland (IE)
  • Chinese University of Hong Kong (HK)
  • McGill University Health Centre (CA)
  • Memorial Sloan Kettering Cancer Center (US)
  • Pfizer (United States) (US)
  • Pfizer (Italy) (IT)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2013-06-20
Volume
368
Issue
25
Pages
2385-2394
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1214886
OpenAlex
W2050249255
Cited by
3,381
References
31
Citations by year
2026: 60 · 2025: 100 · 2024: 102 · 2023: 133 · 2022: 173 · 2021: 204 · 2020: 241 · 2019: 261 · 2018: 306 · 2017: 397 · 2016: 436 · 2015: 494 · 2014: 376 · 2013: 91 · 2012: 3
FWCI
378.32
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • 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 › Oncology › Lung Cancer Research Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Keywords
crizotinib, ALK-positive non-small cell lung cancer, ALK rearrangement, tyrosine kinase inhibitors, pemetrexed, docetaxel, progression-free survival, overall survival, quality of life, platinum-based chemotherapy, targeted therapy, metastatic lung cancer, adverse events, visual disturbances
MeSH terms
Pemetrexed, Docetaxel, Crizotinib, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Female, Glutamates, Guanine, Humans, Lung Neoplasms, Male, Middle Aged, Pyrazoles, Pyridines, Quality of Life, Disease-Free Survival, Taxoids, Protein Kinase Inhibitors, Kaplan-Meier Estimate, Young Adult

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