PMID- 31463126 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220410 IS - 2072-1439 (Print) IS - 2077-6624 (Electronic) IS - 2072-1439 (Linking) VI - 11 IP - 7 DP - 2019 Jul TI - Efficacy and safety of crizotinib in patients with ROS1 rearranged non-small cell lung cancer: a retrospective analysis. PG - 2965-2972 LID - 10.21037/jtd.2019.07.44 [doi] AB - BACKGROUND: Tyrosine kinase inhibitors (TKIs) are remarkably effective in patients with non-small cell lung carcinoma (NSCLC) harboring driver gene mutations and rearrangements. Crizotinib, a small-molecule TKI, has been demonstrated to be an efficacious drug against c-ros oncogene 1-rearranged NSCLC (ROS1-NSCLC) in clinical trials. However, information regarding the use of crizotinib in clinical practice in Japan is limited. METHODS: Subjects with a definite diagnosis of advanced/relapsed ROS1-NSCLC were selected from consecutive NSCLC patients treated at the National Cancer Center Hospital between December 2014 and May 2018. We retrospectively assessed the efficacy and safety of crizotinib in clinical practice. RESULTS: Among 24 patients with ROS1-NSCLC, the ROS1 rearrangement status was assessed using reverse transcription polymerase chain reaction (RT-PCR) (n=17), fluorescence in situ hybridization (FISH) (n=8), or next-generation sequencing (n=5) (some overlap occurred). Thirteen patients were treated with crizotinib in clinical practice. Among the 10 patients in whom clinical efficacy could be evaluated, the objective response rate (ORR) was 80.0% [95% confidence interval (CI), 49.0 to 94.3]. The median follow-up time was 35.5 months (95% CI, 8.9 to 44.6), the median progression-free survival (PFS) time was 10.0 months (95% CI, 5.1 to 27.0), and the median overall survival (OS) time was 28.7 months (95% CI, 6.7 to not reached). The most common adverse events were an aspartate/alanine aminotransferase (AST/ALT) increased and vision disorder. No severe adverse events related to crizotinib occurred. CONCLUSIONS: The use of crizotinib in patients with ROS1-NSCLC was effective and well tolerated in clinical practice in Japan without severe adverse events. FAU - Masuda, Ken AU - Masuda K AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Fujiwara, Yutaka AU - Fujiwara Y AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. AD - Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan. FAU - Shinno, Yuki AU - Shinno Y AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Mizuno, Takaaki AU - Mizuno T AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Sato, Jun AU - Sato J AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Morita, Ryo AU - Morita R AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Matsumoto, Yuji AU - Matsumoto Y AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Murakami, Shuji AU - Murakami S AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Goto, Yasushi AU - Goto Y AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Kanda, Shintaro AU - Kanda S AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Horinouchi, Hidehito AU - Horinouchi H AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. FAU - Yamamoto, Noboru AU - Yamamoto N AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. AD - Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan. FAU - Ohe, Yuichiro AU - Ohe Y AD - Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. LA - eng PT - Journal Article PL - China TA - J Thorac Dis JT - Journal of thoracic disease JID - 101533916 PMC - PMC6688037 OTO - NOTNLM OT - C-ros oncogene 1 (ROS1) OT - crizotinib OT - non-small cell lung carcinoma (NSCLC) OT - tyrosine kinase inhibitors (TKIs) COIS- Conflicts of Interest: Dr. Fujiwara reports grants from Abbvie, grants and personal fees from Astra Zeneca, grants and personal fees from BMS, grants from Chugai, grants from Daiichi-Sankyo, grants from Eisai, grants from Eli Lilly, grants from Incyte, grants from Merck Serono, grants and personal fees from MSD, grants and personal fees from Novartis, personal fees from ONO, personal fees from Sysmex, personal fees from Taiho, outside the submitted work. Dr. Matsumoto reports grants from Hitachi, grants from Hitachi High-Technologies, grants from Boston Scientific, personal fees from Olympus, personal fees from Cook Medical, personal fees from AstraZeneca, outside the submitted work. Dr. Murakami reports grants from Takeda Pharmaceutical, personal fees from Astrazeneca, personal fees from Chugai Pharmaceutical, personal fees from Boehringer Ingelheim, personal fees from Taiho Pharmaceutical, personal fees from Ono Pharmaceutical, outside the submitted work. Dr. Goto reports grants and personal fees from Eli Lilly, personal fees from Chugai, grants and personal fees from Taiho Pharmaceutical, personal fees from Boehringer Ingelheim, personal fees from Pfizer, personal fees from Novartis, personal fees from Glaxo Smith Kline, personal fees from AstraZeneca, grants and personal fees from Ono Pharmaceutical, grants and personal fees from Bristol Myers Squibb, personal fees from Shionogi Pharma, personal fees from Merck Sharp and Dohme, grants from Abbvie, from null, outside the submitted work. Dr. Kanda reports grants and personal fees from AstraZeneca, grants and personal fees from Ono Pharmaceutical, grants from AbbVie, personal fees from Bristol-Myers Squibb, personal fees from Chugai, outside the submitted work. Dr. Horinouchi reports grants and non-financial support from Ono, during the conduct of the study; grants and personal fees from BMS, grants and personal fees from Novartis, grants from Astellas, grants and personal fees from Taiho, grants and personal fees from Chugai, personal fees from Lilly, grants and personal fees from Astra Zeneca, grants and personal fees from MSD, grants from Merck Serono, grants from Genomic Health, outside the submitted work. Dr. Yamamoto reports grants from Chugai, grants from Taiho, grants from Eisai, grants from Lilly, grants from Quintiles, grants from Astellas, grants from BMS, grants from Novartis, grants from Daiichi-Sankyo, grants from Pfizer, grants from Boehringer Ingelheim, grants from Kyowa-Hakko Kirin, grants from Bayer, grants from ONO PHARMACEUTICAL CO., LTD, grants from Takeda, personal fees from ONO PHARMACEUTICAL CO., LTD, personal fees from Chugai, personal fees from AstraZeneca, personal fees from Pfizer, personal fees from Lilly, personal fees from BMS, personal fees from Eisai, personal fees from Otsuka, personal fees from Takeda, personal fees from Boehringer Ingelheim, personal fees from Cimic, grants from Janssen Pharma, grants from MSD, grants from Merck, outside the submitted work. Dr. Ohe reports grants and personal fees from Pfizer, during the conduct of the study; grants and personal fees from AstraZeneca, grants and personal fees from Chugai, grants and personal fees from ONO, personal fees from Celltrion, personal fees from Amgen, grants and personal fees from Kyorin, grants and personal fees from Takeda, grants and personal fees from Lilly, grants and personal fees from BMS, grants and personal fees from MSD, personal fees from Boehringer Ingelheim, grants and personal fees from Taiho, grants from Kissei, personal fees from Novartis, grants from Dainippon-Sumitomo, grants from Ignyta, outside the submitted work. The other authors have no conflicts of interest to declare. EDAT- 2019/08/30 06:00 MHDA- 2019/08/30 06:01 PMCR- 2019/07/01 CRDT- 2019/08/30 06:00 PHST- 2019/08/30 06:00 [entrez] PHST- 2019/08/30 06:00 [pubmed] PHST- 2019/08/30 06:01 [medline] PHST- 2019/07/01 00:00 [pmc-release] AID - jtd-11-07-2965 [pii] AID - 10.21037/jtd.2019.07.44 [doi] PST - ppublish SO - J Thorac Dis. 2019 Jul;11(7):2965-2972. doi: 10.21037/jtd.2019.07.44.