Kentaro Ito1, Takeharu Yamanaka2, Hidetoshi Hayashi3, Yoshihiro Hattori4, Kazumi Nishino5, Haruki Kobayashi6, Yuko Oya7, Toshihide Yokoyama8, Takashi Seto9, Koichi Azuma10, Tomoya Fukui11, Toshiyuki Kozuki12, Atsushi Nakamura13, Kentaro Tanaka14, Katsuya Hirano15, Takashi Yokoi16, Haruko Daga17, Shinya Sakata18, Daichi Fujimoto19, Masahide Mori20, Ken Maeno21, Takuya Aoki22, Atsuhisa Tamura23, Satoru Miura24, Satoshi Watanabe25, Hiroaki Akamatsu26, Osamu Hataji1, Kensuke Suzuki27, Shigeto Hontsu28, Koji Azuma29, Akihiro Bessho30, Akihito Kubo31, Motoyasu Okuno32, Kazuhiko Nakagawa3, Nobuyuki Yamamoto33. 1. Respiratory Center, Matsusaka Municipal Hospital, 1550 Tonomachi, Matsusaka City, Mie, 515-0073, Japan. 2. Department of Biostatistics, Yokohama City University School of Medicine, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa, 236-0027, Japan. 3. Department of Medical Oncology, Kindai University Faculty of Medicine, 3-4-1 Kowakae, Higashiosaka City, Osaka, 577-8502, Japan. 4. Department of Thoracic Oncology, Hyogo Cancer Center, 13-70 Kitaoujicho, Akashi, Hyogo, 673-8558, Japan. 5. Department of Thoracic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka-shi, Osaka, 541-8567, Japan. 6. Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimo-Nagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan. 7. Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku Nagoya, 464-8681, Japan. 8. Department of Respiratory Medicine, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan. 9. Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, 3-1-1 Minami-ku, Fukuoka-shi, Fukuoka, 811-1395, Japan. 10. Division of Respirology, Neurology, and Rheumatology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan. 11. Department of Respiratory Medicine, Kitasato University School of Medicine, 1-15-1 Kitazato, Minami, Sagamihara, Kanagawa, 252-0374, Japan. 12. Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemotocho, Matsuyama, Ehime, 791-0280, Japan. 13. Respiratory Medicine, Sendai Kousei Hospital, 4-15 Hirose-cho, Aoba-ku, Sendai City, Miyagi, 980-0873, Japan. 14. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka City, 812-8582, Japan. 15. Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77, Higashinaniwacho, Amagashiki City, Hyogo, 660-8550, Japan. 16. Department of Thoracic Oncology, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. 17. Department of Medical Oncology, Osaka City General Hospital, 2-13-22 Miyakojima-hondori, Miyakojima-ku, Osaka, 534-0021, Japan. 18. Department of Respiratory Medicine, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto-shi, 860-8556, Japan. 19. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan; Internal Medicine III, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8509, Japan. 20. Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1, Toneyama, Toyonaka-city, Osaka, 560-8552, Japan. 21. Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan. 22. Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan. 23. Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose, Tokyo, 204-8585, Japan. 24. Department of Internal Medicine, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata City, Niigata, 951-8566, Japan. 25. Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuoku, Niigata, 951-8510, Japan. 26. Internal Medicine III, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8509, Japan. 27. Internal Medicine, Toyama Prefectural Central Hospital, 2-2-78, Nishinagae, Toyama-shi, Toyama, 930-8550, Japan. 28. Department of Respiratory Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. 29. Respiratory Division, Department of Internal Medicine, Itami City Hospital, 1-100 Koyaike, Itami City, Hyogo, 664-8540, Japan. 30. Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, 2-1-1 Aoe, Kita-ku, Okayama, Okayama, 700-8607, Japan. 31. Division of Respiratory Medicine and Allergology, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan. 32. Department of Respiratory Medicine, Okazaki City Hospital, 3-1, Kouryuuji Town Gosyoai, Okazaki City, Aichi, 444-8553, Japan. 33. Internal Medicine III, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8509, Japan. Electronic address: nbyamamo@wakayama-med.ac.jp.
Abstract
BACKGROUND: The data of sequential therapy of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) in clinical practice have been limited. METHODS: We reviewed the clinical data of patients with ALK-rearranged non-small cell lung cancer who received crizotinib (CRZ) or alectinib (ALEC) between May 2012 and December 2016. Patients were divided into two groups based on the first-administered ALK-TKI, the CRZ or ALEC group. The combined time-to-treatment failure (TTF) was defined as the sum of the 'TTF of CRZ' plus the 'TTF of ALEC' if patients were treated with CRZ followed by ALEC in the CRZ group. The primary end-point is the comparison between the combined TTF and the TTF of ALEC in the ALEC group. RESULTS: Of 864 patients enrolled from 61 institutions, 840 patients were analysed. There were 535 of 305 patients in the CRZ/ALEC groups. The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group (median, 34.4 versus 27.2 months; hazard ratio [HR], 0.709; P = 0.0044). However, there was no significant difference in overall survival (OS) between the patients who received ALEC after CRZ in the CRZ group and the patients in the ALEC group (median, 88.4 months versus. not reached; HR, 1.048; P = 0.7770). In the whole population, the CRZ group had a significantly shorter OS than the ALEC group (median, 53.6 months versus not reached; HR, 1.821, P < 0.0001). CONCLUSION: The combined TTF in the CRZ group was significantly longer than the TTF in the ALEC group; however, OS benefit of sequential therapy against ALEC as the first ALK-TKI was not shown.
BACKGROUND: The data of sequential therapy of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) in clinical practice have been limited. METHODS: We reviewed the clinical data of patients with ALK-rearranged non-small cell lung cancer who received crizotinib (CRZ) or alectinib (ALEC) between May 2012 and December 2016. Patients were divided into two groups based on the first-administered ALK-TKI, the CRZ or ALEC group. The combined time-to-treatment failure (TTF) was defined as the sum of the 'TTF of CRZ' plus the 'TTF of ALEC' if patients were treated with CRZ followed by ALEC in the CRZ group. The primary end-point is the comparison between the combined TTF and the TTF of ALEC in the ALEC group. RESULTS: Of 864 patients enrolled from 61 institutions, 840 patients were analysed. There were 535 of 305 patients in the CRZ/ALEC groups. The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group (median, 34.4 versus 27.2 months; hazard ratio [HR], 0.709; P = 0.0044). However, there was no significant difference in overall survival (OS) between the patients who received ALEC after CRZ in the CRZ group and the patients in the ALEC group (median, 88.4 months versus. not reached; HR, 1.048; P = 0.7770). In the whole population, the CRZ group had a significantly shorter OS than the ALEC group (median, 53.6 months versus not reached; HR, 1.821, P < 0.0001). CONCLUSION: The combined TTF in the CRZ group was significantly longer than the TTF in the ALEC group; however, OS benefit of sequential therapy against ALEC as the first ALK-TKI was not shown.