Toshikazu Moriwaki1, Shota Fukuoka2, Toshiki Masuishi3, Atsuo Takashima4, Yosuke Kumekawa5, Takeshi Kajiwara6, Kentaro Yamazaki7, Taito Esaki8, Akitaka Makiyama9, Tadamichi Denda10, Yukimasa Hatachi11, Takeshi Suto12, Naotoshi Sugimoto13, Masanobu Enomoto14, Toshiaki Ishikawa15, Tomomi Kashiwada16, Eiji Oki17, Yoshito Komatsu18, Akihito Tsuji19, Kenji Tsuchihashi20, Daisuke Sakai21, Hideki Ueno22, Takao Tamura23, Kimihiro Yamashita24, Yasuhiro Shimada25. 1. Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8575, Japan. tmoriwak@gmail.com. 2. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, 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. Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan. 11. Department of Medical Oncology, Kobe City Medical Center General Hospital, Hyogo, Japan. 12. Department of Gastroenterological Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan. 13. Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan. 14. Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo, Japan. 15. Department of Specialized Surgeries, Tokyo Medical and Dental University, Graduate School of Medicine and Dentistry, Tokyo, Japan. 16. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan. 17. Department Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 18. Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Hokkaido, Japan. 19. Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kagawa, Japan. 20. Department of Medicine and Biosystemic Science, Kyushu University Graduate of Medical Sciences, Fukuoka, Japan. 21. Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Osaka, Japan. 22. Department of Surgery, National Defense Medical College Hospital, Saitama, Japan. 23. Department of Medical Oncology, Kindai University, Faculty of Medicine, Osaka, Japan. 24. Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan. 25. Clinical Oncology Division, Kochi Health Sciences Center, Kochi, Japan.
Abstract
BACKGROUND: Although regorafenib or trifluridine/tipiracil (FTD/TPI) has been recognized as a later-line standard treatment in patients with metastatic colorectal cancer (mCRC), not all patients have beneficial outcomes. This study aimed to develop a prognostic scoring system for evaluating the overall survival (OS) benefit. METHODS: Patients included in the REGOTAS study, which comprised 489 patients (regorafenib group: 199; FTD/TPI group: 290 patients), were evaluated. OS was analyzed using multivariate Cox proportional model. The prognostic score was calculated using the worst four individual factors weighted by hazard ratio, and the total scores were categorized as low-, moderate-, and high-OS benefit. RESULTS: The worst four factors in the regorafenib group were AST > 40 IU/dL (point, + 3), CRP ≥ 1.0 mg/dL (+ 2), number of metastatic organ site ≥ 3 (+ 2), and duration from initiation of 1st-line chemotherapy < 18 months (+ 2), while they were AST (+ 2), CRP (+ 2), CA19-9 > 37.0 U/mL (+ 2), and ECOG PS ≥ 1 (+ 2) in the FTD/TPI group. These corresponded to a total prognostic score of > 5, 2-4, and 0 points in the regorafenib group and 8, 2-6, and 0 points in the FTD/TPI group. The median OS in the low, moderate, and high OS benefit group was 3.3 (95% CI 3.0-3.7), 8.1 (95% CI 6.4-9.7), and 12.6 months (95% CI 10.6-14.6) in the regorafenib group and 2.8 (95% CI 2.0-3.5), 7.5 (95% CI 6.6-8.3), and 15.4 months (95% CI 9.7-21.2) in the FTD/TPI group. CONCLUSION: These prognostic scores are useful for identifying patients with mCRC who will obtain survival benefits from these drugs.
BACKGROUND: Although regorafenib or trifluridine/tipiracil (FTD/TPI) has been recognized as a later-line standard treatment in patients with metastatic colorectal cancer (mCRC), not all patients have beneficial outcomes. This study aimed to develop a prognostic scoring system for evaluating the overall survival (OS) benefit. METHODS:Patients included in the REGOTAS study, which comprised 489 patients (regorafenib group: 199; FTD/TPI group: 290 patients), were evaluated. OS was analyzed using multivariate Cox proportional model. The prognostic score was calculated using the worst four individual factors weighted by hazard ratio, and the total scores were categorized as low-, moderate-, and high-OS benefit. RESULTS: The worst four factors in the regorafenib group were AST > 40 IU/dL (point, + 3), CRP ≥ 1.0 mg/dL (+ 2), number of metastatic organ site ≥ 3 (+ 2), and duration from initiation of 1st-line chemotherapy < 18 months (+ 2), while they were AST (+ 2), CRP (+ 2), CA19-9 > 37.0 U/mL (+ 2), and ECOG PS ≥ 1 (+ 2) in the FTD/TPI group. These corresponded to a total prognostic score of > 5, 2-4, and 0 points in the regorafenib group and 8, 2-6, and 0 points in the FTD/TPI group. The median OS in the low, moderate, and high OS benefit group was 3.3 (95% CI 3.0-3.7), 8.1 (95% CI 6.4-9.7), and 12.6 months (95% CI 10.6-14.6) in the regorafenib group and 2.8 (95% CI 2.0-3.5), 7.5 (95% CI 6.6-8.3), and 15.4 months (95% CI 9.7-21.2) in the FTD/TPI group. CONCLUSION: These prognostic scores are useful for identifying patients with mCRC who will obtain survival benefits from these drugs.
Authors: Robert J Mayer; Eric Van Cutsem; Alfredo Falcone; Takayuki Yoshino; Rocio Garcia-Carbonero; Nobuyuki Mizunuma; Kentaro Yamazaki; Yasuhiro Shimada; Josep Tabernero; Yoshito Komatsu; Alberto Sobrero; Eveline Boucher; Marc Peeters; Ben Tran; Heinz-Josef Lenz; Alberto Zaniboni; Howard Hochster; James M Cleary; Hans Prenen; Fabio Benedetti; Hirokazu Mizuguchi; Lukas Makris; Masanobu Ito; Atsushi Ohtsu Journal: N Engl J Med Date: 2015-05-14 Impact factor: 91.245
Authors: Axel Grothey; Eric Van Cutsem; Alberto Sobrero; Salvatore Siena; Alfredo Falcone; Marc Ychou; Yves Humblet; Olivier Bouché; Laurent Mineur; Carlo Barone; Antoine Adenis; Josep Tabernero; Takayuki Yoshino; Heinz-Josef Lenz; Richard M Goldberg; Daniel J Sargent; Frank Cihon; Lisa Cupit; Andrea Wagner; Dirk Laurent Journal: Lancet Date: 2012-11-22 Impact factor: 79.321
Authors: Jakob Michael Riedl; Florian Posch; Florian Moik; Angelika Bezan; Joanna Szkandera; Maria Anna Smolle; Anne-Katrin Kasparek; Martin Pichler; Herbert Stöger; Michael Stotz; Armin Gerger Journal: Oncotarget Date: 2017-10-04
Authors: Antoine Adenis; Christelle de la Fouchardiere; Bernard Paule; Pascal Burtin; David Tougeron; Jennifer Wallet; Louis-Marie Dourthe; Pierre-Luc Etienne; Laurent Mineur; Stéphanie Clisant; Jean-Marc Phelip; Andrew Kramar; Thierry Andre Journal: BMC Cancer Date: 2016-07-07 Impact factor: 4.430