TY - JOUR
T1 - Phase Ib/II Study of Biweekly TAS-102 in Combination with Bevacizumab for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies (BiTS Study)
AU - Satake, Hironaga
AU - Kato, Takeshi
AU - Oba, Koji
AU - Kotaka, Masahito
AU - Kagawa, Yoshinori
AU - Yasui, Hisateru
AU - Nakamura, Masato
AU - Watanabe, Takanori
AU - Matsumoto, Toshihiko
AU - Kii, Takayuki
AU - Terazawa, Tetsuji
AU - Makiyama, Akitaka
AU - Takano, Nao
AU - Yokota, Mitsuru
AU - Okita, Yoshihiro
AU - Matoba, Koreatsu
AU - Hasegawa, Hiroko
AU - Tsuji, Akihito
AU - Komatsu, Yoshito
AU - Yoshino, Takayuki
AU - Yamazaki, Kentaro
AU - Mishima, Hideyuki
AU - Oki, Eiji
AU - Nagata, Naoki
AU - Sakamoto, Junichi
N1 - Funding Information:
The authors thank the patients and families who participated in this study, as well as the members of the Data and Safety Monitoring Committee (Yoshihiro Kakeji, Keiji Hirata, and Kei Muro). The study content was presented in part at the European Society for Medical Oncology Asia 2018 Congress, Singapore, November 23–25, 2018; the 2019 Gastrointestinal Cancers Symposium, San Francisco, CA, January 17–19, 2019; and the 2020 Gastrointestinal Cancers Symposium, San Francisco, CA, January 23–25, 2020. This study was supported in part by the nonprofit organization Epidemiological and Clinical tResearch Information Network. Editorial assistance and English editing were provided by Guy Harris of DMC Corp.
Publisher Copyright:
© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
PY - 2020/12
Y1 - 2020/12
N2 - Lessons Learned: A biweekly TAS-102 plus BEV schedule in patients with heavily pretreated mCRC showed equivalent efficacy with less toxicity compared with the current schedule of TAS-102 plus BEV combination. Biweekly TAS-102 plus BEV combination could reduce unnecessary dose reduction of TAS-102, maintain higher doses, and possibly be effective even in cases without chemotherapy-induced neutropenia (CIN). The prespecified subgroup analysis of this study showed an obvious association between CIN within the first two cycles and prognosis of biweekly TAS-102 plus BEV. Background: TAS-102 (trifluridine/tipiracil) plus bevacizumab (BEV) combination therapy has shown promising activity in patients with metastatic colorectal cancer (mCRC). However, the previously reported dose and schedule for the TAS-102 (70 mg/m2/day on days 1–5 and 8–12, every 4 weeks) plus BEV (5 mg/kg on day 1, every 2 weeks) regimen is complicated by severe hematological toxicities and difficult administration schedules. Here, we evaluated the efficacy and safety of a more convenient biweekly TAS-102 plus BEV combination. Methods: Patients with mCRC who were refractory or intolerant to standard chemotherapies were enrolled. Patients received biweekly TAS-102 (twice daily on days 1–5, every 2 weeks) with BEV (5mg/kg on day 1, every 2 weeks). The primary endpoint was progression-free survival rate at 16 weeks (16-w PFS rate). Results: From October 2017 to January 2018, 46 patients were enrolled. The recommended phase II dose was determined to be TAS-102 (70 mg/m2/day). Of the 44 eligible patients, the 16-w PFS rate was 40.9% (95% confidence interval, 26.3%–56.8%), and the null hypothesis was rejected (p <.0001). Median progression-free survival (PFS) and overall survival were 4.29 months and 10.86 months, respectively. Disease control rate was 59.1%. Common grade 3 or higher adverse events were hypertension (40.9%), neutropenia (15.9%), and leucopenia (15.9%). Conclusion: Biweekly TAS-102 plus BEV showed promising antitumor activity with safety.
AB - Lessons Learned: A biweekly TAS-102 plus BEV schedule in patients with heavily pretreated mCRC showed equivalent efficacy with less toxicity compared with the current schedule of TAS-102 plus BEV combination. Biweekly TAS-102 plus BEV combination could reduce unnecessary dose reduction of TAS-102, maintain higher doses, and possibly be effective even in cases without chemotherapy-induced neutropenia (CIN). The prespecified subgroup analysis of this study showed an obvious association between CIN within the first two cycles and prognosis of biweekly TAS-102 plus BEV. Background: TAS-102 (trifluridine/tipiracil) plus bevacizumab (BEV) combination therapy has shown promising activity in patients with metastatic colorectal cancer (mCRC). However, the previously reported dose and schedule for the TAS-102 (70 mg/m2/day on days 1–5 and 8–12, every 4 weeks) plus BEV (5 mg/kg on day 1, every 2 weeks) regimen is complicated by severe hematological toxicities and difficult administration schedules. Here, we evaluated the efficacy and safety of a more convenient biweekly TAS-102 plus BEV combination. Methods: Patients with mCRC who were refractory or intolerant to standard chemotherapies were enrolled. Patients received biweekly TAS-102 (twice daily on days 1–5, every 2 weeks) with BEV (5mg/kg on day 1, every 2 weeks). The primary endpoint was progression-free survival rate at 16 weeks (16-w PFS rate). Results: From October 2017 to January 2018, 46 patients were enrolled. The recommended phase II dose was determined to be TAS-102 (70 mg/m2/day). Of the 44 eligible patients, the 16-w PFS rate was 40.9% (95% confidence interval, 26.3%–56.8%), and the null hypothesis was rejected (p <.0001). Median progression-free survival (PFS) and overall survival were 4.29 months and 10.86 months, respectively. Disease control rate was 59.1%. Common grade 3 or higher adverse events were hypertension (40.9%), neutropenia (15.9%), and leucopenia (15.9%). Conclusion: Biweekly TAS-102 plus BEV showed promising antitumor activity with safety.
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U2 - 10.1634/theoncologist.2020-0643
DO - 10.1634/theoncologist.2020-0643
M3 - Article
C2 - 32666647
AN - SCOPUS:85088877883
VL - 25
SP - e1855-e1863
JO - Oncologist
JF - Oncologist
SN - 1083-7159
IS - 12
ER -
