Benjamin J Solomon1, Federico Cappuzzo2, Enriqueta Felip2, Fiona H Blackhall2, Daniel B Costa2, Dong-Wan Kim2, Kazuhiko Nakagawa2, Yi-Long Wu2, Tarek Mekhail2, Jolanda Paolini2, Jennifer Tursi2, Tiziana Usari2, Keith D Wilner2, Paulina Selaru2, Tony S K Mok2. 1. 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. 2. 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.
Abstract
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 two subgroups was low.
RCT Entities:
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 two subgroups was low.
Authors: Francesco Facchinetti; Marcello Tiseo; Massimo Di Maio; Paolo Graziano; Emilio Bria; Giulio Rossi; Silvia Novello Journal: Transl Lung Cancer Res Date: 2016-06