Crizotinib versus Chemotherapy in Asian Patients with ALK-Positive Advanced Non-small Cell Lung Cancer

Cancer Research and Treatment 2018³â 50±Ç 3È£ p.691 ~ p.700

(Nishio Makoto) - Cancer Institute Hospital of JFCR Thoracic Oncology Center
±èµ¿¿Ï(Kim Dong-Wan) - Seoul National University Hospital Department of Internal Medicine
(Wu Yi-Long) - Guangdong Lung Cancer Institute
(Nakagawa Kazuhiko) - Kindai University
(Solomon Benjamin J.) - Peter MacCallum Cancer Centre
(Shaw Alice T.) - Massachusetts General Hospital
(Hashigaki Satoshi) - Pfizer Oncology
(Ohki Emiko) - Pfizer Oncology
(Usari Tiziana) - Pfizer Oncology
(Paolini Jolanda) - Pfizer Oncology
(Polli Anna) - Pfizer Oncology
(Wilner Keith D.) - Pfizer Oncology
(Mok Tony) - University of Hong Kong Hong Kong Cancer Institute State Key Laboratory of South China

Abstract

Purpose: Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib in Asian subpopulations of two global phase III trials.

Materials and Methods: This analysis evaluated previously treated and untreated patients in two randomized, open-label phase III trials of crizotinib versus chemotherapy in ALK-positive advanced NSCLC in second-line (PROFILE 1007) and first-line settings (PROFILE 1014). Efficacy and safety were analyzed by race in the intention-to-treat and ¡°as-treated¡± populations for efficacy and safety endpoints, respectively.

Results: In previously treated (n=157) and untreated (n=157) Asian patients, PFS was statistically significantly longer with crizotinib versus chemotherapy (hazard ratio for PFS, 0.526; 95% confidence interval, 0.363 to 0.762; p < 0.001 and hazard ratio, 0.442; 95% confidence interval, 0.302 to 0.648; p < 0.001, respectively). Similar antitumor activity was seen in the non-Asian and overall populations. ORRs were statistically significantly higher with crizotinib versus chemotherapy in both Asian and non-Asian previously treated and untreated patients (p < 0.05). The most common treatment-emergent adverse events (any grade)with crizotinib were vision disorder, diarrhea, and nausea, which were observed at a comparable incidence across Asian and non-Asian populations, irrespective of previous treatment status. Most adverse events were mild to moderate in severity.

Conclusion: These data, currently the only analysis showing Asian and non-Asian populations in the same study, support the efficacy and safety of crizotinib in Asian patients with previously treated or untreated ALK-positive advanced NSCLC.

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Asia, Carboplatin, Cisplatin, Crizotinib, Non-small cell lung carcinoma, Pemetrexed
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In comparison with chemotherapy, crizotinib significantly prolonged PFS and increased ORRs.
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