Medline ® Abstract for Reference 47
of 'Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer'
Intracranial Efficacy of Crizotinib Versus Chemotherapy in Patients With Advanced ALK-Positive Non-Small-Cell Lung Cancer: Results From PROFILE 1014.
Solomon BJ, Cappuzzo F, Felip E, Blackhall FH, Costa DB, Kim DW, Nakagawa K, Wu YL, Mekhail T, Paolini J, Tursi J, Usari T, Wilner KD, Selaru P, Mok TS
J Clin Oncol. 2016;34(24):2858. Epub 2016 Mar 28.
PURPOSE: Intracranial efficacy of first-line crizotinib versus chemotherapy was compared prospectively in the phase III PROFILE 1014 study in ALK-positive non-small-cell lung cancer.
PATIENTS AND METHODS: Patients were randomly assigned to receive crizotinib (250 mg twice daily; n = 172) or chemotherapy (pemetrexed 500 mg/m(2) plus cisplatin 75 mg/m(2) or carboplatin at area under the curve 5 to 6, every 3 weeks for≤six cycles; n = 171). Patients with stable treated brain metastases (tBM) were eligible. Intracranial efficacy was assessed at baseline and every 6 or 12 weeks in patients with or without known brain metastases (BM), respectively; intracranial time to tumor progression (IC-TTP; per protocol) and intracranial disease control rate (IC-DCR; post hoc) were measured. The intent-to-treat population was also assessed.
RESULTS: Of 343 patients in the intent-to-treat population, 23% had tBM at baseline. A nonsignificant IC-TTP improvement was observed with crizotinib in the intent-to-treat population (hazard ratio [HR], 0.60; P = .069), patients with tBM (HR, 0.45; P = .063), and patients without BM (HR, 0.69; P = .323). Among patients with tBM, IC-DCR was significantly higher with crizotinib versus chemotherapy at 12 weeks (85% v 45%, respectively; P<.001) and 24 weeks (56% v 25%, respectively; P = .006). Progression-free survival was significantly longer with crizotinib versus chemotherapy in both subgroups (tBM present: HR, 0.40; P<.001; median, 9.0 v 4.0 months, respectively; BM absent: HR, 0.51; P<.001; median, 11.1 v 7.2 months, respectively) and in the intent-to-treat population (HR, 0.45; P<.001; median, 10.9 v 7.0 months, respectively).
CONCLUSION: Compared with chemotherapy, crizotinib demonstrated a significantly higher IC-DCR in patients with tBM. Improvements in IC-TTP were not statistically significant in patients with or without tBM, although sensitivity to detect treatment differences in or between the twosubgroups was low.
Benjamin J. Solomon, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Federico Cappuzzo, Istituto Toscano Tumori, Livorno; Jolanda Paolini, Jennifer Tursi, and Tiziana Usari, Pfizer Oncology, Milan, Italy; Enriqueta Felip, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain; Fiona H. Blackhall, The Christie Hospital and Institute of Cancer Sciences, Manchester University, Manchester, United Kingdom; Daniel B. Costa, Beth Israel Deaconess Center, Boston, MA; Tarek Mekhail, Florida Hospital Cancer Institute, Orlando, FL; Keith D. Wilner and Paulina Selaru, Pfizer Oncology, La Jolla, CA; Dong-Wan Kim, Seoul National University Hospital, Seoul, South Korea; Kazuhiko Nakagawa, Kinki University, Osaka, Japan; Yi-Long Wu, Guangdong Lung Cancer Institute, Guangzhou, China; and Tony S.K. Mok, State Key Laboratory of South China, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Shatin, China. email@example.com.