Keigo Chida1, Daisuke Kotani1, Toshikazu Moriwaki2, Shota Fukuoka1, Toshiki Masuishi3, Atsuo Takashima4, Yosuke Kumekawa5, Takeshi Kajiwara6, Kentaro Yamazaki7, Masato Komoda8, Akitaka Makiyama9,10, Tadamichi Denda11, Yukimasa Hatachi12, Takeshi Suto13, Naotoshi Sugimoto14, Masanobu Enomoto15, Toshiaki Ishikawa16, Tomomi Kashiwada17, Koji Ando18, Satoshi Yuki19, Yoshihiro Okita20, Hitoshi Kusaba21, Daisuke Sakai22, Koichi Okamoto23, Takao Tamura24, Kimihiro Yamashita25, Masahiko Gosho26, Yasuhiro Shimada27. 1. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 2. Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 3. Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan. 4. Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan. 5. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan. 6. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Ehime, Japan. 7. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 8. Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 9. Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Fukuoka, Japan. 10. Cancer Center, Gifu University Hospital, Gifu, Japan. 11. Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan. 12. Department of Medical Oncology, Kobe City Medical Center General Hospital, Hyogo, Japan. 13. Department of Gastroenterological Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan. 14. Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan. 15. Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan. 16. Department of Specialized Surgeries, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan. 17. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan. 18. Department Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 19. Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan. 20. Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan. 21. Department of Medicine and Comprehensive Biosystemic Science, Kyushu University Graduate of Medical Sciences, Fukuoka, Japan. 22. Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Osaka, Japan. 23. Department of Surgery, National Defense Medical College, Tokorozawa, Japan. 24. Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan. 25. Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan. 26. Department of Biostatistics, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 27. Clinical Oncology Division, Kochi Health Sciences Center, Kochi, Japan.
Abstract
Background: The survival benefits of regorafenib (REG) and trifluridine/tipiracil hydrochloride (TFTD) have been demonstrated in chemorefractory patients with metastatic colorectal cancer (mCRC). However, the effects of crossover administration of REG and TFTD on patient survival remain unclear. The present study evaluated the association between exposure to REG and TFTD and overall survival (OS) in patients with mCRC using data from the REGOTAS study. Patients and Methods: We analyzed patients registered in the REGOTAS study, which retrospectively compared the efficacy and safety of use of REG or TFTD as later-line chemotherapy for chemorefractory mCRC patients. We compared the survival outcomes of cohort A (treated using both REG and TFTD) and cohort B (treated using either REG or TFTD). Results: A total of 550 patients (cohort A, n = 252; cohort B, n = 298) met the inclusion criteria. The median OS was significantly increased in cohort A compared with cohort B [9.6 months (95% confidence interval (CI), 8.9-10.9 months) vs. 5.2 months (95% CI, 4.4-6.0 months), P < 0.001]. Multivariate analysis revealed that cohort A was independently associated with a significant increase in OS [A vs. B: Hazard ratios (HR), 0.58; 95% CI, 0.47-0.72; P < 0.001]. Subgroup analysis adjusted using multivariate Cox model revealed a consistently better trend in most subgroups for cohort A compared with cohort B. Conclusions: Our study revealed prolonged survival in patients treated with REG and TFTD. Therefore, all active agents, including REG and TFTD, should be made available to mCRC patients.
Background: The survival benefits of regorafenib (REG) and trifluridine/tipiracil hydrochloride (TFTD) have been demonstrated in chemorefractory patients with metastatic colorectal cancer (mCRC). However, the effects of crossover administration of REG and TFTD on patient survival remain unclear. The present study evaluated the association between exposure to REG and TFTD and overall survival (OS) in patients with mCRC using data from the REGOTAS study. Patients and Methods: We analyzed patients registered in the REGOTAS study, which retrospectively compared the efficacy and safety of use of REG or TFTD as later-line chemotherapy for chemorefractory mCRC patients. We compared the survival outcomes of cohort A (treated using both REG and TFTD) and cohort B (treated using either REG or TFTD). Results: A total of 550 patients (cohort A, n = 252; cohort B, n = 298) met the inclusion criteria. The median OS was significantly increased in cohort A compared with cohort B [9.6 months (95% confidence interval (CI), 8.9-10.9 months) vs. 5.2 months (95% CI, 4.4-6.0 months), P < 0.001]. Multivariate analysis revealed that cohort A was independently associated with a significant increase in OS [A vs. B: Hazard ratios (HR), 0.58; 95% CI, 0.47-0.72; P < 0.001]. Subgroup analysis adjusted using multivariate Cox model revealed a consistently better trend in most subgroups for cohort A compared with cohort B. Conclusions: Our study revealed prolonged survival in patients treated with REG and TFTD. Therefore, all active agents, including REG and TFTD, should be made available to mCRC patients.