Kenji Tsuchihashi1, Mamoru Ito1, Toshikazu Moriwaki2, Shota Fukuoka3, Hiroya Taniguchi4, Atsuo Takashima5, Yosuke Kumekawa6, Takeshi Kajiwara7, Kentaro Yamazaki8, Taito Esaki9, Akitaka Makiyama10, Tadamichi Denda11, Hironaga Satake12, Takeshi Suto13, Naotoshi Sugimoto14, Kenji Katsumata15, Toshiaki Ishikawa16, Tomomi Kashiwada17, Eiji Oki18, Yoshito Komatsu19, Hiroyuki Okuyama20, Daisuke Sakai21, Hideki Ueno22, Takao Tamura23, Kimihiro Yamashita24, Junji Kishimoto25, Yasuhiro Shimada26, Eishi Baba27. 1. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. 2. Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. 3. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. 4. Department of Clinical Oncology, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Aichi, Japan. 5. Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan. 6. Department of Gastroenterology, Saitama Cancer Center, Ina-machi, Kitaadachi-gun, Saitama, Japan. 7. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Minamiumemoto-machi, Matsuyama, Ehime, Japan. 8. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan. 9. Department of Gastrointestinal and Medical Oncology, National Kyushu Cancer Center, Minami-ku, Fukuoka, Fukuoka, Japan. 10. Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Yahatanishi-ku, Kitakyushu, Fukuoka, Japan. 11. Division of Gastroenterology, Chiba Cancer Center, Chuo-ku, Chiba, Chiba, Japan. 12. Department of Medical Oncology, Kobe City Medical Center General Hospital, Chuo-ku, Kobe, Hyogo, Japan. 13. Department of Gastroenterological Surgery, Yamagata Prefectural Central Hospital, Yamagata, Yamagata, Japan. 14. Department of Medical Oncology, Osaka International Cancer Institute, Chuo-ku, Osaka, Osaka, Japan. 15. Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan. 16. Department of Specialized Surgeries, Tokyo Medical and Dental University, Graduate School of Medicine and Dentistry, Bunkyo-ku, Tokyo, Japan. 17. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Saga, Japan. 18. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Fukuoka, Japan. 19. Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Kita-ku, Sapporo, Hokkaido, Japan. 20. Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Miki-cho, Kita-gun, Kagawa, Japan. 21. Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. 22. Department of Surgery, National Defense Medical College Hospital, Tokorozawa, Saitama, Japan. 23. Department of Medical Oncology, Kindai University, Faculty of Medicine, Osaka-Sayama, Osaka, Japan. 24. Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Chuo-ku, Kobe, Hyogo, Japan. 25. Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan. 26. Clinical Oncology Division, Kochi Health Sciences Center, Kochi, Kochi, Japan. 27. Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. Electronic address: e-baba@intmed1.med.kyushu-u.ac.jp.
Abstract
BACKGROUND: Assessment of patient factors is essential for selecting later-line chemotherapy in patients with metastatic colorectal cancer (mCRC). The efficacy, prognosis, and safety of each treatment regimen according to nutritional and inflammatory status still remain to be elucidated. PATIENTS AND METHODS: A total of 550 patients with mCRC who were registered in the REGOTAS study (Regorafenib versus TAS-102 as Salvage-line in patients with colorectal cancer refractory to standard chemotherapies: a multicenter observational study, UMIN 000020416) and treated with trifluridine/tipiracil (TFTD) or regorafenib as a later-line therapy were retrospectively stratified according to the modified Glasgow Prognostic Score (mGPS), which divided patients into mGPS 0 to 2 by serum albumin and C-reactive protein, and compared. RESULTS: The median overall survival (OS) of patients with mGPS 0, 1, and 2 was 10.0 months (95% confidence interval [CI], 9.2-11.6 months), 6.5 months (95% CI, 5.3-7.1 months), and 3.9 months (95% CI, 3.3-4.9 months), respectively. The median progression-free survival (PFS) with mGPS 0, 1, and 2 was 2.5 months (95% CI, 2.1-3.0 months), 2.0 months (95% CI, 1.9-2.3 months), and 1.7 months (95% CI, 1.4-1.9 months), respectively. There were significant differences by mGPS in both OS and PFS (all P < .001). No significant differences in OS and PFS were observed between the patient groups treated with TFTD and regorafenib in each mGPS group. In patients aged ≥ 65 years with mGPS 2, the OS and PFS were worse with regorafenib than with TFTD (OS: hazard ratio, 1.45; 95% CI, 0.93-2.25; P = .097; PFS: hazard ratio, 1.57, 95% CI, 1.01-2.44; P = .047), but there were no consistent trends observed as mGPS increased. The frequency of grade 3 and more adverse events was generally similar in each mGPS group. The multivariate analyses showed that mGPS was the strongest predictive factor for OS. CONCLUSIONS: The mGPS before later-line chemotherapy is strongly correlated with survival in patients with mCRC.
BACKGROUND: Assessment of patient factors is essential for selecting later-line chemotherapy in patients with metastatic colorectal cancer (mCRC). The efficacy, prognosis, and safety of each treatment regimen according to nutritional and inflammatory status still remain to be elucidated. PATIENTS AND METHODS: A total of 550 patients with mCRC who were registered in the REGOTAS study (Regorafenib versus TAS-102 as Salvage-line in patients with colorectal cancer refractory to standard chemotherapies: a multicenter observational study, UMIN 000020416) and treated with trifluridine/tipiracil (TFTD) or regorafenib as a later-line therapy were retrospectively stratified according to the modified Glasgow Prognostic Score (mGPS), which divided patients into mGPS 0 to 2 by serum albumin and C-reactive protein, and compared. RESULTS: The median overall survival (OS) of patients with mGPS 0, 1, and 2 was 10.0 months (95% confidence interval [CI], 9.2-11.6 months), 6.5 months (95% CI, 5.3-7.1 months), and 3.9 months (95% CI, 3.3-4.9 months), respectively. The median progression-free survival (PFS) with mGPS 0, 1, and 2 was 2.5 months (95% CI, 2.1-3.0 months), 2.0 months (95% CI, 1.9-2.3 months), and 1.7 months (95% CI, 1.4-1.9 months), respectively. There were significant differences by mGPS in both OS and PFS (all P < .001). No significant differences in OS and PFS were observed between the patient groups treated with TFTD and regorafenib in each mGPS group. In patients aged ≥ 65 years with mGPS 2, the OS and PFS were worse with regorafenib than with TFTD (OS: hazard ratio, 1.45; 95% CI, 0.93-2.25; P = .097; PFS: hazard ratio, 1.57, 95% CI, 1.01-2.44; P = .047), but there were no consistent trends observed as mGPS increased. The frequency of grade 3 and more adverse events was generally similar in each mGPS group. The multivariate analyses showed that mGPS was the strongest predictive factor for OS. CONCLUSIONS: The mGPS before later-line chemotherapy is strongly correlated with survival in patients with mCRC.