PMID- 33249761 OWN - NLM STAT- MEDLINE DCOM- 20210719 LR - 20210719 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 10 IP - 2 DP - 2021 Jan TI - Trifluridine/tipiracil plus bevacizumab as a first-line treatment for elderly patients with metastatic colorectal cancer (KSCC1602): A multicenter phase II trial. PG - 454-461 LID - 10.1002/cam4.3618 [doi] AB - BACKGROUND: A previous Phase I/II study demonstrated that TAS-102 (trifluridine/tipiracil [FTD/TPI]) plus bevacizumab (Bev) has encouraging efficacy and controllable safety for patients with previously treated metastatic colorectal cancer. Therefore, we designed for assessing the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer. METHODS: This is a multicenter, single-arm Phase II study included patients >/=70 years old with previously untreated, unresectable metastatic colorectal cancer. Treatment consisted of FTD/TPI plus Bev given every 4 weeks. The primary endpoint was progression-free survival (PFS), assuming a null hypothesis of a PFS of 5 months. The secondary endpoints were the overall survival (OS), overall response rate (ORR), and adverse events (AEs). RESULTS: Between 5 January 2017 and 13 March 2018, 39 patients were enrolled from 18 institutions. The median patient age was 76.0 years (range, 70-88); the ECOG-PS was 0 in 24 patients and 1 in 15 patients. The median PFS was 9.4 months as a primary endpoint, and the median OS was 22.4 months. The ORR was 40.5% and the disease control rate was 86.5%. Grade 3-4 AEs included neutropenia (71.8%), leukopenia (51.3%), anorexia (15.4%), febrile neutropenia (10.3%), and fatigue (10.3%). CONCLUSIONS: FTD/TPI plus Bev is an effective and well-tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer. Capecitabine/bevacizumab can be selected as a subsequent maintenance therapy without irinotecan and oxaliplatin because FTD/TPI has no cross-resistance with 5-fluorouracil. CLINICAL TRIAL REGISTRATION: UMIN clinical trials registry (UMIN000025241). CI - (c) 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Oki, Eiji AU - Oki E AUID- ORCID: 0000-0002-9763-9366 AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Makiyama, Akitaka AU - Makiyama A AD - Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Kitakyushu, Japan. AD - Cancer Center, Gifu University Hospital, Gifu, Japan. FAU - Miyamoto, Yuji AU - Miyamoto Y AD - Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medicine, Kumamoto, Japan. FAU - Kotaka, Masahiko AU - Kotaka M AD - Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan. FAU - Kawanaka, Hirofumi AU - Kawanaka H AD - Department of Surgery, National Hospital Organization Beppu Medical Center, Beppu, Japan. FAU - Miwa, Keisuke AU - Miwa K AD - Department of Surgery, Kurume University Hospital, Kurume, Japan. FAU - Kabashima, Akira AU - Kabashima A AD - Department of Surgery, National Hospital Organization Oita Medical Center, Oita, Japan. FAU - Noguchi, Tomohiro AU - Noguchi T AD - Department of Surgery, Imakiire General Hospital, Kagoshima, Japan. FAU - Yuge, Kotaro AU - Yuge K AD - Department of Surgery, Social Insurance Tagawa Hospital, Tagawa, Japan. FAU - Kashiwada, Tomomi AU - Kashiwada T AD - Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University, Saga, Japan. FAU - Ando, Koji AU - Ando K AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Shimokawa, Mototsugu AU - Shimokawa M AD - Department of Biostatistics, Yamaguchi University, Yamaguchi, Japan. FAU - Saeki, Hiroshi AU - Saeki H AD - Department of Gastroenterological Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan. FAU - Akagi, Yoshito AU - Akagi Y AD - Department of Surgery, Kurume University Hospital, Kurume, Japan. FAU - Baba, Hideo AU - Baba H AUID- ORCID: 0000-0002-3183-3115 AD - Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medicine, Kumamoto, Japan. FAU - Maehara, Yoshihiko AU - Maehara Y AD - Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan. FAU - Mori, Masaki AU - Mori M AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20201129 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (Pyrrolidines) RN - 2S9ZZM9Q9V (Bevacizumab) RN - NGO10K751P (tipiracil) RN - QR26YLT7LT (Thymine) RN - RMW9V5RW38 (Trifluridine) SB - IM EIN - Cancer Med. 2021 Jun;10(11):3836. PMID: 33988315 MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Bevacizumab/administration & dosage MH - Colorectal Neoplasms/*drug therapy/pathology MH - Female MH - Follow-Up Studies MH - Humans MH - Male MH - Prognosis MH - Pyrrolidines/administration & dosage MH - Survival Rate MH - Thymine/administration & dosage MH - Trifluridine/administration & dosage PMC - PMC7877360 OTO - NOTNLM OT - Trifluridine OT - bevacizumab OT - colorectal cancer OT - elderly OT - thymidine phosphorylase inhibitor COIS- Eiji Oki has received honoraria for lecturing from Taiho Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.; Merck Serono; Takeda Pharmaceutical Co., Ltd.; and Chugai Pharmaceutical Co., Ltd. Akitaka Makiyama reports personal fees from Lily; personal fees from Chugai; and personal fees from Takeda, outside the submitted work. Masahito Kotaka reports other from Chugai Pharmaceutical Co., Ltd.; other from Yakult Honsha Co., Ltd.; other from Takeda Pharmaceutical Company Limited; other from Merck Biopharma Co., Ltd.; and other from Taiho Pharmaceutical Co., Ltd., outside the submitted work. Hideo Baba reports grants, personal fees, and nonfinancial support from Taiho Pharmaceutical Co., Ltd.; grants and nonfinancial support from Merck Biopharma Co., Ltd., during the conduct of the study; grants, personal fees, and nonfinancial support from Ono Pharmaceutical Co., Ltd.; grants, personal fees, and nonfinancial support from Eli Lilly Japan K.K.; grants and personal fees from Takeda Pharmaceutical Co., Ltd.; grants and personal fees from Chugai Pharmaceutical Co., Ltd.; grants from Shionogi & Co., Ltd.; grants from Covidien Japan Inc.; grants and nonfinancial support from Yakult Honsha Co., Ltd.; grants from Shin Nippon Biomedical Laboratories, Ltd.; grants from Novartis-pharma K.K.; grants from Toyama Chemical Co., Ltd.; and grants and nonfinancial support from Johnson & Johnson K.K., outside the submitted work. Masaki Mori reports grants, personal fees, and nonfinancial support from Taiho Pharmaceutical Co., Ltd. The other authors have no conflicts of interest to declare. This work has been previously presented and published in abstract form as follows: - Oki E., et al. Trifluridine/tipiracil plus bevacizumab in elderly patients with previously untreated metastatic colorectal cancer (KSCC1602): A multicenter, Phase II clinical trial. J Clin Oncol. 2019; 37(15): https://doi.org/10.1200/JCO.2019.37.15_suppl.3548 - Makiyama A., et al. Bevacizumab plus trifluridine/tipiracil in elderly patients with previously untreated metastatic colorectal cancer (KSCC 1602): A single-arm, Phase II study. Ann Oncol. 2019; 30, Suppl. 5:234-235. https://doi.org/10.1093/annonc/mdz246.097 EDAT- 2020/11/30 06:00 MHDA- 2021/07/20 06:00 PMCR- 2020/11/29 CRDT- 2020/11/29 20:39 PHST- 2020/09/19 00:00 [received] PHST- 2020/11/02 00:00 [accepted] PHST- 2020/11/30 06:00 [pubmed] PHST- 2021/07/20 06:00 [medline] PHST- 2020/11/29 20:39 [entrez] PHST- 2020/11/29 00:00 [pmc-release] AID - CAM43618 [pii] AID - 10.1002/cam4.3618 [doi] PST - ppublish SO - Cancer Med. 2021 Jan;10(2):454-461. doi: 10.1002/cam4.3618. Epub 2020 Nov 29.