First-line crizotinib versus chemotherapy in ALK-positive lung cancer

Benjamin J. Solomon, Tony Mok, Dong Wan Kim, Yi Long Wu, Kazuhiko Nakagawa, Tarek Mekhail, Enriqueta Felip, Federico Cappuzzo, Jolanda Paolini, Tiziana Usari, Shrividya Iyer, Arlene Reisman, Keith D. Wilner, Jennifer Tursi, Fiona Blackhall

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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 bodysurface 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 number, NCT01154140.).

Original languageEnglish
Pages (from-to)2167-2177
Number of pages11
JournalNew England Journal of Medicine
Issue number23
StatePublished - 4 Dec 2014

Cite this

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. (2014). First-line crizotinib versus chemotherapy in ALK-positive lung cancer. New England Journal of Medicine, 371(23), 2167-2177.