Yoichiro Yoshida1, Takeshi Yamada2, Hirohiko Kamiyama3, Chihiro Kosugi4, Keiichiro Ishibashi5, Hiroshi Yoshida2, Hideyuki Ishida5, Satoru Yamaguchi6, Hidekazu Kuramochi7, Atsuko Fukazawa8, Hiromichi Sonoda9, Kazuhiko Yoshimatsu10, Akihisa Matsuda11, Suguru Hasegawa12, Kazuhiro Sakamoto3, Toshiaki Otsuka13, Keiji Koda4. 1. Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. yyoshida@fukuoka-u.ac.jp. 2. Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan. 3. Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University, Tokyo, Japan. 4. Department of Surgery, Teikyo University Chiba Medical Center, Chiba, Japan. 5. Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan. 6. Department of Surgical Oncology, Dokkyo Medical University, Tochigi, Japan. 7. Department of Chemotherapy, Tokyo Women's Medical University Yachiyo Medical Center, Chiba, Japan. 8. Department of Gastroenterological Surgery, Iwata City Hospital, Shizuoka, Japan. 9. Department of Surgery, Shiga University of Medical Science, Shiga, Japan. 10. Department of Surgery, Saiseikai Kurihashi Hospital, Saitama, Japan. 11. Department of Surgery, Nippon Medical School Chiba Hokuso Hospital, Chiba, Japan. 12. Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. 13. Dept of Hygiene and Public Health, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Abstract
BACKGROUND: TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets. METHODS: This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1-5 and 8-12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety. RESULTS: Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred. CONCLUSIONS: This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.
BACKGROUND:TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets. METHODS: This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRCpatients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1-5 and 8-12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety. RESULTS: Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred. CONCLUSIONS: This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.
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