Article (Scientific journals)
First-line crizotinib versus chemotherapy in ALK-positive lung cancer.
Solomon, Benjamin J.; Mok, Tony; Kim, Dong-Wan et al.
2014In New England Journal of Medicine, 371 (23), p. 2167-77
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Keywords :
Adenocarcinoma/drug therapy/mortality; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use; Carboplatin/administration & dosage; Carcinoma, Non-Small-Cell Lung/drug therapy/mortality; Cisplatin/administration & dosage; Disease-Free Survival; Female; Glutamates/administration & dosage; Guanine/administration & dosage/analogs & derivatives; Humans; Kaplan-Meier Estimate; Lung Neoplasms/drug therapy/mortality; Male; Middle Aged; Protein Kinase Inhibitors/adverse effects/therapeutic use; Pyrazoles/adverse effects/therapeutic use; Pyridines/adverse effects/therapeutic use; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors
Abstract :
[en] 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.).
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Solomon, Benjamin J.
Mok, Tony
Kim, Dong-Wan
Wu, Yi-Long
Nakagawa, Kazuhiko
Mekhail, Tarek
Felip, Enriqueta
Cappuzzo, Federico
Paolini, Jolanda
Usari, Tiziana
Iyer, Shrividya
Reisman, Arlene
Wilner, Keith D.
Tursi, Jennifer
Blackhall, Fiona
More authors (5 more) Less
Other collaborator :
Louis, Renaud ;  Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie
Language :
English
Title :
First-line crizotinib versus chemotherapy in ALK-positive lung cancer.
Publication date :
04 December 2014
Journal title :
New England Journal of Medicine
ISSN :
0028-4793
eISSN :
1533-4406
Publisher :
Massachusetts Medical Society, United States - Massachusetts
Volume :
371
Issue :
23
Pages :
2167-77
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 16 January 2015

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