528P - The randomized phase III study of bi-weekly trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) vs. FTD/TPI monotherapy for chemorefractory metastatic colorectal cancer (mCRC): 1-year follow-up updated data from JCOG2014 (ROBiTS)

Background

Based on the SUNLIGHT trial, FTD/TPI plus BEV combination has been regarded as standard therapy in the late-line treatment for patients with mCRC. However, the combination of FTD/TPI plus BEV increased the frequency of hematologic toxicity. JCOG2014 is a phase III trial to confirm the superiority of bi-weekly (1 week-on, 1 week-off) FTD/TPI plus BEV combination over 4-week intervals (2 weeks-on, 2 weeks-off) FTD/TPI monotherapy. An initial report was presented at ASCO-GI 2024. Here, we present survival outcomes with adequate observation.

Methods

We randomly assigned, in a 1:1 ratio, patients who were refractory or intolerant to standard chemotherapy for the treatment of mCRC to receive 4-week intervals FTD/TPI 70 mg/m²/day monotherapy (arm A) or bi-weekly FTD/TPI plus bevacizumab 5 mg/kg (arm B). The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), response rate (RR), disease control rate (DCR), and safety.

Results

This study was terminated early based on the SUNLIGHT trial. Between January 2022 and February 2023, a total of 152 patients were randomized (75 in the arm A and 77 in the arm B). Baseline characteristics were well balanced. With a median follow-up of 16.9 months for surviving patients, the median OS was 13.0 vs. 10.6 months (hazard ratio [HR], 0.919; 95% confidence interval [CI], 0.617 to 1.369) and the median PFS was 2.4 vs. 4.0 months (HR, 0.544; 95% CI, 0.387 to 0.763). RR was 1.3% vs. 5.3% and DCR was 45.3% vs. 53.3%. The most common Grade 3 or higher adverse events in each arm were neutropenia (46.6% vs. 23.7%), anemia (15.1% vs. 3.9%), fatigue (2.7% vs. 7.9%), anorexia (5.5% vs. 5.3%), nausea (5.5% vs. 5.3%), hypertension (4.1% vs. 3.9%) and febrile neutropenia (4.1% vs. 0%).

Conclusions

Bi-weekly FTD/TPI plus BEV combination in late-line mCRC extends PFS and reduces hematologic toxicity compared to 4-week intervals FTD/TPI monotherapy, though no survival benefit was observed.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Colorectal Cancer Study Group of Japan Clinical Oncology Group (JCOG).

Funding

National Cancer Center Research and Development Funds (29-A-3, 2020-J-3) National Cancer Center Research and Development Funds (29-A-3, 2020-J-3) National Cancer Center Research and Development Funds (29-A-3, 2020-J-3) National Cancer Center Research and Development Funds (29-A-3, 2020-J-3).

Disclosure

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., Novartis Pharma; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co. Ltd., Daiichi Sankyo, Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Sanofi; Financial Interests, Institutional, Local PI: Asahi Kasei; Non-Financial Interests, Member: ASCO, JSMO. 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. T. Tsushima: Financial Interests, Personal, Invited Speaker: Taiho Pharma, Ono Pharmaceutical, MSD, Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Taiho Pharma, MSD, Ono Pharmaceutical. S. Boku: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb, MSD Japan, Eisai Co., Ltd., Nippon Kayaku Co.,Ltd., Asahi Kasei Pharma Co.; Financial Interests, Institutional, Funding: Kyo Diagnostics Co., Ltd.. A. Takashima: Financial Interests, Personal, Invited Speaker: Lilly, Taiho Pharmaceutical, Ono Pharmaceutical, Takeda, Chugai Pharmaceutical, Merck; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical, Takeda, Merck Sharp & Dohme, Bristol-Myers Squibb, Sumitomo Dainippon Pharma, Isofol Medical AB, Incyte; Financial Interests, Personal, Research Grant: Pfizer Inc, Daiichi Sankyo, Hutchison MediPharma. M. Asayama: Financial Interests, Personal, Invited Speaker: Chugai, Takeda, Merck Biopharma, Ono, Taiho; Financial Interests, Personal and Institutional, Research Funding: Isofol Medical AB, SYSMEX, Seagen. H. Yasui: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Chugai Pharma, Bristol-Myers Squibb, Daiichi-Sankyo, Terumo, Eli Lilly Japan, Merck Biopharma, Yakult Honsha, Bayer Yakuhin, Takeda Pharmaceutical; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Institutional, Local PI: MSD, Daiichi-Sankyo, Ono Pharmaceutical, Astellas Pharma, Amgen, AstraZeneca. Y. Kito: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Ono Pharmaceutical. T. Hamaguchi: Financial Interests, Institutional, Local PI: ONO Pharmaceutical Co., Ltd.; Other, honorary: ONO Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.