523P - A phase II study of intrapatient dose escalation of biweekly trifluridine/tipiracil plus bevacizumab for colorectal cancer (E-BiTS study)

Background

Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) is a standard treatment for refractory metastatic colorectal cancer (mCRC). The biweekly regimen has shown promise in phase 2 studies, especially in reducing neutropenia. However, the optimal biweekly dosage of FTD/TPI remains undetermined. Notably, FTD/TPI showed higher efficacy in patients with neutropenia, leading to the customized intrapatient dose escalation strategy to enhance efficacy.

Methods

Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) is a standard treatment for refractory metastatic colorectal cancer (mCRC). The biweekly regimen has shown promise in phase 2 studies, especially in reducing neutropenia. However, the optimal biweekly dosage of FTD/TPI remains undetermined. Notably, FTD/TPI showed higher efficacy in patients with neutropenia, leading to the customized intrapatient dose escalation strategy to enhance efficacy.

Results

Thirty-six patients were enrolled; two were excluded for not meeting the eligibility criteria. Patient characteristics (n = 34) included a median age of 65 years (range: 39–75), 76% with ECOG PS 0, 82% with left-sided cancer, 59% with RAS mutation, and 74% with 2 or more metastatic organs. Dose escalation of FTD/TPI at least 1 level was feasible in 91% of the patients. The maximum FTD/TPI levels of +1, +2, and +3 were achieved in 41%, 29%, and 21% of patients, respectively. The median relative dose intensity of FTD/TPI during the first 4 cycles was 98.9% among those who received ≥4 cycles (n = 29). The DCR was 72.7% (80% confidence interval: 60.4–82.8). Median progression-free survival was 5.8 months (95% CI: 2.7–6.5), and overall survival was not reached with median follow up time of 12.6 months. Any grade and grade ≥3 neutropenia rates were 74% and 24%, respectively. Other adverse events were in line with previous studies.

Conclusions

The E-BiTS study achieved its primary endpoint with a DCR of 72.7%. Intrapatient dose escalation of biweekly FTD/TPI plus BEV was well-tolerated and effective in patients with mCRC.

Clinical trial identification

jRCTs041220085.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

H. Taniguchi: Financial Interests, Personal, Invited Speaker: Ono, Takeda, Eli Lilly, Chugai, Taiho, Merck Biopharma, Amgen, MSD K.K, Bristol Myers Squibb Japan, Roche Diagnostics; Financial Interests, Institutional, Coordinating PI: Takeda, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Ono. S. Yuki: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Eli Lilly K.K., Takeda Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd, Bristol-Myers Squibb Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Miyarisan Pharmaceutical Co., Ltd.. H. Takeda: Financial Interests, Personal, Invited Speaker: Taiho, MSD, BMS, Chugai. S. Mitani: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co., Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical Co.; Financial Interests, Personal, Research Grant: Caris Life Science. A. Makiyama: Financial Interests, Personal, Invited Speaker: Eli Lilly, Taiho, Ono, Daiichi-Sankyo, Bristol Myers Squibb. T. Kudo: Financial Interests, Personal, Invited Speaker: Merck Biopharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K., MSD Co., Ltd., Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Daiichi Sankyo Co., Ltd.; Financial Interests, Institutional, Local PI: Astellas Pharma Inc., Novartis Pharma K.K., Amgen inc., Ono Pharmaceutical Co., Ltd., MSD Co., Ltd., AstraZeneca K.K., Incyte Biosciences Japan G.K.; Financial Interests, Institutional, Research Grant: Pfizer Inc.. K. Mori: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Eli Lilly Japan, Chugai Pharma. K. Muro: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Ono, Chugai, Astellas; Financial Interests, Personal, Invited Speaker: Eli Lilly, Ono, Daiichi Sankyo, Taiho, Bristol Myers Squibb, Takeda, MSD; Financial Interests, Institutional, Research Grant, Including local PI as role: Astellas, Amgen, Sanofi, Daiichi Sankyo, Taiho, MSD, Pfizer, Merck Biopharma, Eisai, Ono, Novartis, PRA Health Sciences Inc., Parexel International Inc.; Financial Interests, Personal, Steering Committee Member: Chugai, AstraZeneca, Amgen; Non-Financial Interests, Principal Investigator: Takeda. All other authors have declared no conflicts of interest.