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J Clin Oncol. 2018 Aug 1;36(22):2251-2258. doi: 10.1200/JCO.2017.77.4794. Epub 2018 May 16.

Final Overall Survival Analysis From a Study Comparing First-Line Crizotinib Versus Chemotherapy in ALK-Mutation-Positive Non-Small-Cell Lung Cancer.

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Benjamin J. Solomon, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Dong-Wan Kim, Seoul National University Hospital, Seoul, Republic of Korea; Yi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou; Tony S. Mok, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China; Kazuhiko Nakagawa, Kindai University Faculty of Medicine, Osaka, Japan; Tarek Mekhail, Florida Hospital, Orlando, FL; Enriqueta Felip, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain; Federico Cappuzzo, Azienda Unità Sanitaria Locale Della Romagna, Ravenna; Jolanda Paolini and Tiziana Usari, Pfizer Oncology, Milan, Italy; Yiyun Tang and Keith D. Wilner, Pfizer Oncology, La Jolla, CA; and Fiona Blackhall, Manchester University, and Christie Hospital National Health Service Foundation Trust, Manchester, United Kingdom.


Purpose The phase III PROFILE 1014 trial compared crizotinib with chemotherapy as first-line treatment in patients with anaplastic lymphoma kinase (ALK) -positive advanced nonsquamous non-small-cell lung cancer. Here, we report the final overall survival (OS) results. Patients and Methods Patients were randomly assigned to receive oral crizotinib 250 mg twice daily (n = 172) or intravenous pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin (area under the concentration-time curve of 5 to 6 mg·mL/min) every 3 weeks for a maximum of six cycles (n = 171). Crossover to crizotinib was permitted after disease progression. OS was analyzed using a stratified log-rank test and a prespecified rank-preserving structural failure time model to account for crossover. Results Median follow-up duration for OS was approximately 46 months for both arms. In the chemotherapy arm, 144 patients (84.2%) received crizotinib in subsequent lines. Hazard ratio for OS was 0.760 (95% CI, 0.548 to 1.053; two-sided P = .0978). Median OS was not reached (NR) with crizotinib (95% CI, 45.8 months to NR) and 47.5 months with chemotherapy (95% CI, 32.2 months to NR). Survival probability at 4 years was 56.6% (95% CI, 48.3% to 64.1%) with crizotinib and 49.1% (95% CI, 40.5% to 57.1%) with chemotherapy. After crossover adjustment, there was an improvement in OS that favored crizotinib (hazard ratio, 0.346; 95% bootstrap CI, 0.081 to 0.718). The longest OS was observed in crizotinib-treated patients who received a subsequent ALK tyrosine kinase inhibitor. No new safety signals were identified. Conclusion The final analysis of the PROFILE 1014 study provides a new benchmark for OS in patients with ALK-rearranged non-small-cell lung cancer and highlights the benefit of crizotinib for prolonging survival in this patient population.


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