Final overall survival analysis from the phase III J-ALEX study of alectinib versus crizotinib in ALK inhibitor-naïve Japanese patients with ALK -positive non-small-cell lung cancer ☆

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K. Hotta¹  T. Hida²  H. Nokihara³  M. Morise⁴  Y.H. Kim⁵  K. Azuma⁶  T. Seto⁷  Y. Takiguchi⁸  M. Nishio⁹  H. Yoshioka^1,10  T. Kumagai^1,11  S. Watanabe^1,12  K. Goto^1,13  M. Satouchi^1,14  T. Kozuki^1,15  T. Shukuya^1,16  K. Nakagawa^1,17  T. Mitsudomi^1,18  N. Yamamoto^1,19  T. Asakawa^2,20  T. Yoshimoto^2,20  S. Takata^2,21  T. Tamura^2,22 

[1] Center for Innovative Clinical Medicine, Okayama University Hospital;Department of Thoracic Oncology, Aichi Cancer Center;Department of Thoracic Oncology, National Cancer Center Hospital;Department of Respiratory Medicine, Nagoya University Graduate School of Medicine;Department of Respiratory Medicine, Kyoto University;Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine;Department of Thoracic Oncology, National Hospital Organization Kyusyu Cancer Center;Department of Medical Oncology, Graduate School of Medicine, Chiba University;Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research;Department of Thoracic Oncology, Kansai Medical University Hospital;Department of Thoracic Oncology, Osaka International Cancer Institute;Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences;Department of Thoracic Oncology, National Cancer Center Hospital East;Department of Thoracic Oncology, Hyogo Cancer Center;Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center;Department of Respiratory Medicine, Juntendo University;Department of Medical Oncology, Kindai University Faculty of Medicine;Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine;Third Department of Internal Medicine, Wakayama Medical University;Biometrics Department, Chugai Pharmaceuticals Co. Ltd;Oncology Clinical Development Department, Chugai Pharmaceuticals Co. Ltd;Thoracic Center, St. Luke’s International Hospital

关键词: alectinib;    ALK-positive NSCLC;    crizotinib;    J-ALEX;    overall survival;   

DOI  :  10.1016/j.esmoop.2022.100527

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Mature progression-free survival (PFS) data from the phase III J-ALEX study showed superiority for alectinib versus crizotinib [hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.26-0.52; median PFS 34.1 versus 10.2 months, respectively] in advanced ALK (anaplastic lymphoma kinase)-positive non-small-cell lung cancer (NSCLC). Overall survival (OS) data were immature (HR 0.80, 99.8799% CI 0.35-1.82) at the time of data cut-off (30 June 2018). We report final OS data after ≥5 years of follow-up.Patients and methods ALK inhibitor naive Japanese patients who were chemotherapy naive or had received one prior chemotherapy regimen were enrolled. Patients were randomized to receive alectinib 300 mg (n = 103) or crizotinib 250 mg (n = 104) twice daily until progressive disease, unacceptable toxicity, death, or withdrawal. The primary endpoint was independent review facility-assessed PFS, with OS (not fully powered) as a secondary endpoint.Results Median duration of OS follow-up was 68.6 months with alectinib and 68.0 months with crizotinib. Treatment with alectinib did not prolong OS relative to crizotinib (HR 1.03, 95.0405% CI 0.67-1.58; P = 0.9105). Five-year OS rates were 60.9% (95% CI 51.4-70.3) with alectinib and 64.1% (95% CI 54.9-73.4) with crizotinib. In total, 91.3% (n = 95/104) of crizotinib-treated patients and 46.6% (n = 48/103) of alectinib-treated patients received at least one subsequent anticancer therapy. After study drug discontinuation, 78.8% of patients in the crizotinib arm switched to alectinib, while 10.7% of patients in the alectinib arm switched to crizotinib as a first subsequent anticancer therapy. Patients randomized to crizotinib tended to switch treatment earlier than those randomized to alectinib.Conclusion Final OS analysis from J-ALEX did not show superiority of alectinib to crizotinib; this result was most likely confounded by treatment crossover. Alectinib remains a standard of care for the treatment of patients with advanced ALK-positive NSCLC.

【 授权许可】

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