Phase II study of trifluridine/tipiracil plus bevacizumab by RAS mutation status in patients with metastatic colorectal cancer refractory to standard therapies: JFMC51-1702-C7.

BACKGROUND

Although the efficacy of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) against metastatic colorectal cancer (mCRC) has been demonstrated, little is known about its effectiveness upon disease stratification by RAS mutations. In this phase II study, we investigated the efficacy and safety profiles of FTD/TPI in mCRC according to RAS mutation status.

PATIENTS AND METHODS

Eligible patients were mCRC refractory or intolerant to all standard therapies other than FTD/TPI and regorafenib. Patients received 4-week cycles of treatment with FTD/TPI (35 mg/m

RESULTS

Between January and September 2018, 102 patients were enrolled, and 97 patients fulfilled the eligibility criteria (48 in the RAS WT cohort and 49 in the RAS MUT cohort). DCRs in the RAS WT and MUT cohort were 66.7% [90% confidence interval (CI), 53.9%-77.8%, P = 0.0013] and 55.1% (90% CI, 42.4%-67.3%, P = 0.0780), respectively. The median progression-free survival (PFS) and overall survival (OS) were 3.8 and 9.3 months, respectively, in the RAS WT cohort and 3.5 and 8.4 months, respectively, in the RAS MUT cohort. The most common grade 3 or higher adverse event in both cohorts was neutropenia (46% in the RAS WT cohort and 62% in the RAS MUT cohort), without unexpected safety signals.

CONCLUSIONS

FTD/TPI plus bevacizumab showed promising activity with an acceptable safety profile for pretreated mCRC, regardless of RAS mutation status, although the efficacy outcomes tended to be better in RAS WT.

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure TT has received research funding from Yakult Honsha and lecture fees from Takeda Pharmaceutical, Sanofi, Taiho Pharmaceutical, Chugai Pharmaceutical, and Yakult Honsha. KY has received honoraria from Bayer, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Merck Serono, Taiho Pharmaceutical, Takeda Pharmaceutical, Yakult Honsha, Sanofi Pharmaceutical, Ono Pharmaceutical, MSD, and Bristol-Myers Squibb. EO has received lecture fees from Chugai Pharmaceutical, Eli Lilly, Merck Biopharma, Taiho Pharmaceutical, and Takeda Pharmaceutical. AM has received personal fees from Chugai Pharmaceutical, Eli Lilly, and Takeda Pharmaceutical. YK has received personal fees from Chugai Pharmaceutical, Eli Lilly, Merck, Sanofi Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, and Yakult Honsha. MA has received research funding from Takeda Pharmaceutical. KO has received personal fees from Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Ono Pharmaceutical, and Takeda Pharmaceutical. TY has received research funding from Chugai Pharmaceutical, Daiichi Sankyo, GlaxoSmithKline, MSD, Novartis Pharma, Ono Pharmaceutical, PAREXEL International, Sanofi, and Sumitomo Dainippon Pharma. KY has received research funding from Abbot, AbbVie, Asahi Kasei Pharma, Astellas, Biogen Japan, Celgene, Covidien Japan, Daiichi Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, KCI, Koninklijke Philips, Kyowa Kirin, Meiji Seika Pharma, Merck Serono, MSD, Nippon Kayaku, Novartis, Ono Pharmaceutical, Otsuka Pharmaceutical, Sanofi, Takeda Pharmaceutical, Toray Medical, Tsumura Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, and Taiho Pharmaceutical, and personal fees from Asahi Kasei Pharma, AstraZeneca, Bristol-Myers Squibb, Covidien Japan, Daiichi Sankyo, Denka, EA Pharmaceutical, Eisai, Eli Lilly, Johnson & Johnson, Merck Serono, MSD, Nippon Kayaku, Novartis, Olympus, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Sanofi, Sanwa Kagaku Kenkyusho, SBI Pharmaceutical, Takeda Pharmaceutical, Teijin Pharmaceutical, TERUMO, Tsumura Pharmaceutical, Yakult Honsha, Chugai Pharmaceutical, and Taiho Pharmaceutical. All other authors have declared no conflicts of interest.