Kazuhiko Nakagawa1, Toyoaki Hida2, Hiroshi Nokihara3, Masahiro Morise4, Koichi Azuma5, Young Hak Kim6, Takashi Seto7, Yuichi Takiguchi8, Makoto Nishio9, Hiroshige Yoshioka10, Toru Kumagai11, Katsuyuki Hotta12, Satoshi Watanabe13, Koichi Goto14, Miyako Satouchi15, Toshiyuki Kozuki16, Ryo Koyama17, Tetsuya Mitsudomi18, Nobuyuki Yamamoto19, Takashi Asakawa20, Morihiko Hayashi21, Wakako Hasegawa22, Tomohide Tamura23. 1. Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2, Ohnohigashi, Osaka-sayama, Osaka 589-8511, Japan. Electronic address: nakagawa@med.kindai.ac.jp. 2. Department of Thoracic Oncology, Aichi Cancer Center, 1-1, Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan. Electronic address: 107974@aichi-cc.jp. 3. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: hnokihara@tokushima-u.ac.jp. 4. Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65, Tsurumaicho, Nagoya Showa-ku, Aichi, 466-8550, Japan. Electronic address: morisem@med.nagoya-u.ac.jp. 5. Institution Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume-shi, Fukuoka, 830-0011, Japan. Electronic address: azuma@med.kurume-u.ac.jp. 6. Department of Respiratory Medicine, Kyoto University, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: ekim@kuhp.kyoto-u.ac.jp. 7. Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-Ku, Fukuoka, 811-1395, Japan. Electronic address: setocruise@gmail.com. 8. Department of Medical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. Electronic address: takiguchi@faculty.chiba-u.jp. 9. Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto, Tokyo 135-8550, Japan. Electronic address: mnishio@jfcr.or.jp. 10. Department of Respiratory Medicine, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama 710-8602, Japan. Electronic address: hgyoshioka@gmail.com. 11. Department of Thoracic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae Chuo-ku, Osaka 541-8567, Japan. Electronic address: torukumagai@ybb.ne.jp. 12. Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. Electronic address: khotta@md.okayama-u.ac.jp. 13. Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuouku, Niigata, 951-8510, Japan. Electronic address: satoshi7@med.niigata-u.ac.jp. 14. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. Electronic address: kgoto@east.ncc.go.jp. 15. Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, 13-70, Kitaoji-cho, Akashi, Hyogo, 673-8558, Japan. Electronic address: satouchi@hp.pref.hyogo.jp. 16. Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-machi, Matsuyama City, Ehime Prefecture 791-0280, Japan. Electronic address: tokozuki@shikoku-cc.go.jp. 17. Department of Respiratory Medicine, Juntendo University, 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan. Electronic address: rkoyama@juntendo.ac.jp. 18. Department of Surgery, Division of Thoracic Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, 377-2, Ohnohigashi, Osaka-sayama, Osaka 589-8511, Japan. Electronic address: mitsudom@med.kindai.ac.jp. 19. Internal Medicine III, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-0012, Japan. Electronic address: nbyamamo@wakayama-med.ac.jp. 20. Clinical Information & Intelligence Department, Chugai Pharmaceutical Co. Ltd, 2-1-1 Nihonbashi-Muromachi, Chuo-ku, Tokyo 103-8324, Japan. Electronic address: asakawatks@chugai-pharm.co.jp. 21. Clinical Science & Strategy Department, Chugai Pharmaceutical Co. Ltd, 2-1-1 Nihonbashi-Muromachi, Chuo-ku, Tokyo 103-8324, Japan. Electronic address: hayashimrh@chugai-pharm.co.jp. 22. Clinical Science & Strategy Department, Chugai Pharmaceutical Co. Ltd, 2-1-1 Nihonbashi-Muromachi, Chuo-ku, Tokyo 103-8324, Japan. Electronic address: hasegawawkk@chugai-pharm.co.jp. 23. Thoracic Center, St. Luke's International Hospital, 9-1, Akashi-cho, Chuo-ku, Tokyo 104-8560, Japan. Electronic address: tamuratomohide@gmail.com.
Abstract
OBJECTIVES: The J-ALEX study compared the efficacy and safety of alectinib with crizotinib in Japanese patients with advanced ALK-positive non-small-cell lung cancer (NSCLC). Superiority in independent review facility (IRF)-assessed progression-free survival (PFS) was demonstrated for alectinib at the second pre-planned interim PFS analysis (data cutoff: December 3, 2015; hazard ratio [HR] 0.34, 99.7 % confidence interval [CI]: 0.17-0.71, P < 0.0001). We report final PFS data and the second pre-planned interim analysis of overall survival (OS) and safety (data cutoff: June 30, 2018). METHODS:Patients aged ≥20 years who were ALK inhibitor-naïve and chemotherapy-naïve, or had received one prior chemotherapy regimen, were randomized to receive alectinib 300 mg (n = 103) or crizotinib 250 mg (n = 104) twice daily. The primary end point was IRF-assessed PFS. Secondary end points included OS and safety. All patients entered survival follow-up in July 2018. RESULTS: Median follow-up was 42.4 months for alectinib and 42.2 months for crizotinib. Sustained improvement in IRF-assessed PFS with alectinib was shown (HR 0.37, 95 % CI: 0.26-0.52; median PFS 34.1 months vs 10.2 months crizotinib). At the second interim OS analysis, superiority of alectinib to crizotinib could not be concluded (stratified HR 0.80, 99.8799 % CI: 0.35-1.82, stratified log-rank P = 0.3860; median OS not reached alectinib vs 43.7 months crizotinib). Fewer alectinib-treated patients experienced grade ≥3 adverse events (36.9 % vs 60.6 % crizotinib). CONCLUSIONS: At the final PFS analysis, alectinib continued to demonstrate superiority in IRF-assessed PFS versus crizotinib in ALK-inhibitor-naïve ALK-positive NSCLC, with a favorable safety profile. OS follow-up continues.
RCT Entities:
OBJECTIVES: The J-ALEX study compared the efficacy and safety of alectinib with crizotinib in Japanese patients with advanced ALK-positive non-small-cell lung cancer (NSCLC). Superiority in independent review facility (IRF)-assessed progression-free survival (PFS) was demonstrated for alectinib at the second pre-planned interim PFS analysis (data cutoff: December 3, 2015; hazard ratio [HR] 0.34, 99.7 % confidence interval [CI]: 0.17-0.71, P < 0.0001). We report final PFS data and the second pre-planned interim analysis of overall survival (OS) and safety (data cutoff: June 30, 2018). METHODS:Patients aged ≥20 years who were ALK inhibitor-naïve and chemotherapy-naïve, or had received one prior chemotherapy regimen, were randomized to receive alectinib 300 mg (n = 103) or crizotinib 250 mg (n = 104) twice daily. The primary end point was IRF-assessed PFS. Secondary end points included OS and safety. All patients entered survival follow-up in July 2018. RESULTS: Median follow-up was 42.4 months for alectinib and 42.2 months for crizotinib. Sustained improvement in IRF-assessed PFS with alectinib was shown (HR 0.37, 95 % CI: 0.26-0.52; median PFS 34.1 months vs 10.2 months crizotinib). At the second interim OS analysis, superiority of alectinib to crizotinib could not be concluded (stratified HR 0.80, 99.8799 % CI: 0.35-1.82, stratified log-rank P = 0.3860; median OS not reached alectinib vs 43.7 months crizotinib). Fewer alectinib-treated patients experienced grade ≥3 adverse events (36.9 % vs 60.6 % crizotinib). CONCLUSIONS: At the final PFS analysis, alectinib continued to demonstrate superiority in IRF-assessed PFS versus crizotinib in ALK-inhibitor-naïve ALK-positive NSCLC, with a favorable safety profile. OS follow-up continues.