Phase Ib/II Study of Biweekly TAS-102 in Combination with Bevacizumab for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies (BiTS Study)期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

Phase Ib/II Study of Biweekly TAS-102 in Combination with Bevacizumab for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies (BiTS Study)

Authors:	Hironaga Satake Takeshi Kato Koji Oba Masahito Kotaka Yoshinori Kagawa Hisateru Yasui Masato Nakamura Takanori Watanabe Toshihiko Matsumoto Takayuki Kii Tetsuji Terazawa Akitaka Makiyama Nao Takano Mitsuru Yokota Yoshihiro Okita Koreatsu Matoba Hiroko Hasegawa Akihito Tsuji Yoshito Komatsu Takayuki Yoshino Kentaro Yamazaki Hideyuki Mishima Eiji Oki Naoki Nagata Junichi Sakamoto

Affiliation:	1. Cancer Treatment Center, Kansai Medical University Hospital, Osaka, Japan;2. Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan;3. Department of Biostatistics, The University of Tokyo, Tokyo, Japan;4. Department of Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan;5. Department of Gastrointestinal Surgery, Kansai Rosai Hospital, Amagasaki, Japan;6. Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan;7. Department of Chemotherapy, Aizawa Hospital, Matsumoto, Japan;8. Department of Surgery, Himeji Red Cross Hospital, Himeji, Japan;9. Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan Department of Medical Oncology, Himeji Red Cross Hospital, Himeji, Japan;10. Cancer Chemotherapy Center, Osaka Medical College Hospital, Takatsuki, Japan;11. Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Kitakyushu, Japan Cancer Center, Gifu University Hospital, Gifu, Japan;12. Department of Surgery, Tokai Central Hospital, Kakamigahara, Japan;13. Department of Surgery, Kurashiki Central Hospital, Kurashiki, Japan;14. Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan;15. Department of Gastrointestinal Medicine, Kobe Rosai Hospital, Kobe, Japan;16. Department of Gastroenterology and Hepatology, National Hospital Organization Osaka National Hospital, Osaka, Japan;17. Division of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan;18. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan;19. Department of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan;20. Division of Cancer Center, Aichi Medical University, Aichi, Japan;21. Department of Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;22. Kitakyushu General Hospital, Kitakyushu, Japan;23. Tokai Central Hospital, Kakamigahara, Japan

Abstract:	Lessons Learned A biweekly TAS‐102 plus BEV schedule in patients with heavily pretreated mCRC showed equivalent efficacy with less toxicity compared with the current schedule of TAS‐102 plus BEV combination. Biweekly TAS‐102 plus BEV combination could reduce unnecessary dose reduction of TAS‐102, maintain higher doses, and possibly be effective even in cases without chemotherapy‐induced neutropenia (CIN). The prespecified subgroup analysis of this study showed an obvious association between CIN within the first two cycles and prognosis of biweekly TAS‐102 plus BEV. BackgroundTAS‐102 (trifluridine/tipiracil) plus bevacizumab (BEV) combination therapy has shown promising activity in patients with metastatic colorectal cancer (mCRC). However, the previously reported dose and schedule for the TAS‐102 (70 mg/m²/day on days 1–5 and 8–12, every 4 weeks) plus BEV (5 mg/kg on day 1, every 2 weeks) regimen is complicated by severe hematological toxicities and difficult administration schedules. Here, we evaluated the efficacy and safety of a more convenient biweekly TAS‐102 plus BEV combination.MethodsPatients with mCRC who were refractory or intolerant to standard chemotherapies were enrolled. Patients received biweekly TAS‐102 (twice daily on days 1–5, every 2 weeks) with BEV (5mg/kg on day 1, every 2 weeks). The primary endpoint was progression‐free survival rate at 16 weeks (16‐w PFS rate).ResultsFrom October 2017 to January 2018, 46 patients were enrolled. The recommended phase II dose was determined to be TAS‐102 (70 mg/m²/day). Of the 44 eligible patients, the 16‐w PFS rate was 40.9% (95% confidence interval, 26.3%–56.8%), and the null hypothesis was rejected (p < .0001). Median progression‐free survival (PFS) and overall survival were 4.29 months and 10.86 months, respectively. Disease control rate was 59.1%. Common grade 3 or higher adverse events were hypertension (40.9%), neutropenia (15.9%), and leucopenia (15.9%).ConclusionBiweekly TAS‐102 plus BEV showed promising antitumor activity with safety.

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