Abstract 446TiP
Background
FTD/TPI is widely used as a late-line treatment for patients with mCRC who are refractory or intolerant to standard chemotherapy based on the results of phase III studies RECOURSE (Mayer RJ, N Engl J Med 2015.) and TERRA (Xu J, J Clin Oncol 2018.). More recently, the efficacy of the combination of FTD/TPI and BEV has also been reported, albeit in phase II studies (Kuboki Y, Lancet Oncol 2017. Pfeiffer P. Lancet Oncol 2020.). However, the combination of FTD/TPI and BEV increased the frequency of neutropenia, a dose-limiting toxicity of FTD/TPI, with Grade 3 or higher reported as 44%-72%. On the other hand, phase II studies suggested that modifying the FTD/TPI schedule in combination with BEV from 4-weeks course (2 weeks-on, 2 weeks-off) to bi-weekly dosing (1 week-on, 1 week-off) reduces Grade 3 or higher neutropenia (16%) without reducing efficacy (Satake H, Oncologist 2020. Yoshida Y, ESMO 2019.). Therefore, we commenced a phase III study to confirm the superiority of bi-weekly FTD/TPI plus BEV to 4-weeks intervals FTD/TPI.
Trial design
This study is an open-label. multicenter, randomized phase III trial conducted in Colorectal Cancer Study Group of Japan Clinical Oncology Group (jRCTs031210544). Key eligibility criteria are mCRC, aged >20 years, ECOG PS <1, with measurable lesion, with adequate organ function, and refractory or intolerant to fluoropyrimidine, oxaliplatin, irinotecan, angiogenesis inhibitor, anti-EGFR antibody (if RAS-wild type), BRAF inhibitor and anti-EGFR antibody (if BRAF V600E-mutant), and immune check point inhibitor (if mismatch repair deficient). Patients are randomly assigned (1:1) to receive bi-weekly FTD/TPI plus BEV or 4-weeks intervals FTD/TPI. The primary endpoint is overall survival (OS). The sample size is 420 patients (210 patients/arm) with one-sided alpha 0.05, power 80%, expected median OS of 8 months and 10.5 months (HR 0.76). The first patient was enrolled in Jan 2022.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
K. Yamazaki: Financial Interests, Personal, Invited Speaker: Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Taiho Pharmaceutical, Lilly, Sanofi, Ono Pharmaceutical, MSD, Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical. H. Satake: Financial Interests, Personal, Invited Speaker: Bayer Co., Ltd., Bristol-Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan Co., Ltd., Merck Bio Pharma Co., Ltd., MSD Co., Ltd., Ono Pharmaceutical Co., Ltd., Sanofi Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Co., Ltd., Yakult Honsha Co., Ltd.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co. Ltd., Daiichi Sankyo, Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Sanofi. J. Mizusawa: Financial Interests, Personal, Other, Honoraria: Chugai pharmaceutical, Taiho pharmaceutical; Other, Other, My spouse receives salary.: Pfizer. N. Shibata: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical CO., Ltd., Kyowa Kirin Co., Ltd., Pfizer Japan Inc., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Yakult Honsha Co., Ltd., Taiho Pharmaceutical Co., Bayer Yakuhin, Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Nippon Kayaku Co.,Ltd., Medicon Inc.; Financial Interests, Personal, Expert Testimony: Kyowa Kirin Co., Ltd.. T. Tsushima: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan, Takeda, Taiho Pharma, Ono Pharmaceutical, MSD; Financial Interests, Institutional, Invited Speaker: Taiho Pharma, MSD, Ono Pharmaceutical, BeiGene, Chugai Pharmaceutical. T. Ohta: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb Japan, Chugai Pharma, Teijin Pharma, Takeda Pharmaceutical Company Limited., Taiho Pharmaceutical Co., Ltd., Eisai Co., Ltd., Yakult Honsha; Financial Interests, Personal and Institutional, Invited Speaker: Takeda Pharmaceutical Company Limited.. T. Hamaguchi: Financial Interests, Institutional, Research Grant: Taiho, Chugai; Financial Interests, Personal, Speaker’s Bureau: Taiho, Chugai. All other authors have declared no conflicts of interest.