title: Intracranial Efficacy of Crizotinib Versus Chemotherapy in Patients With Advanced ALK-Positive Non-Small-Cell Lung Cancer: Results From PROFILE 1014.
abstract: 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 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.
  
  
  
  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).
  
  
  
  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 two subgroups was low.
authors.affiliation: 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. ben.solomon@petermac.org.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Solomon
authors.affiliation: 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.
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
authors.affiliation: 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.
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.affiliation: 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.
authors.forename: Fiona H
authors.initials: FH
authors.lastname: Blackhall
authors.affiliation: 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.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Costa
authors.affiliation: 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.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: 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.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Tarek
authors.initials: T
authors.lastname: Mekhail
authors.affiliation: 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.
authors.forename: Jolanda
authors.initials: J
authors.lastname: Paolini
authors.affiliation: 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.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tursi
authors.affiliation: 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.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Usari
authors.affiliation: 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.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Wilner
authors.affiliation: 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.
authors.forename: Paulina
authors.initials: P
authors.lastname: Selaru
authors.affiliation: 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.
authors.forename: Tony S K
authors.initials: TS
authors.lastname: Mok
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D000077547:Crizotinib; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000068437:Pemetrexed; D000077547:Crizotinib; D016190:Carboplatin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D002945:Cisplatin