Crizotinib versus chemotherapy in advanced ALK-positive lung cancer

Shaw, Alice T., Kim, Dong-Wan, Nakagawa, Kazuhiko, Seto, Takashi, Crinó, Lucio, Ahn, Myung-Ju, De Pas, Tommaso, Besse, Benjamin, Solomon, Benjamin J., Blackhall, Fiona, Wu, Yi- Long, Thomas, Michael, O'Byrne, Kenneth J., Moro-Sibilot, Denis, Camidge, D. Ross, Mok, Tony, Hirsh, Vera, Riely, Gregory J., Iyer, Shrividya, & Tassell, Vanessa (2013) Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. New England Journal of Medicine, 368(25), pp. 2385-2394.

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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; number, NCT00932893.) Copyright © 2013 Massachusetts Medical Society.

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ID Code: 65687
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: anaplastic lymphoma kinase, crizotinib, docetaxel, pemetrexed, adult, advanced cancer, aged, ALK positive non small cell lung cancer, alopecia, article, cancer chemotherapy, cancer growth, chemotherapy induced emesis, constipation, controlled study, death, diarrhea, dizziness, drug efficacy, drug eruption, drug response, drug safety, dysgeusia, dyspnea, edema, fatigue, female, human, lung non small cell cancer, major clinical study, male, nausea, overall survival, phase 3 clinical trial, priority journal, progression free survival, quality of life, randomized controlled trial, self report, side effect, symptom, upper respiratory tract infection, visual disorder, Aged, 80 and over, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Disease-Free Survival, Glutamates, Guanine, Humans, Kaplan-Meier Estimate, Lung Neoplasms, Middle Aged, Protein Kinase Inhibitors, Pyrazoles, Pyridines, Taxoids, Young Adult
DOI: 10.1056/NEJMoa1214886
ISSN: 0028-4793
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2013 Massachusetts Medical Society
Deposited On: 06 Jan 2014 05:32
Last Modified: 08 Jan 2014 02:29

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