Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: the randomized TASCO1 study

Abstract

Background: We designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT-B) and capecitabine plus bevacizumab (C-B) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies.

Patients and methods: From 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TT-B (N = 77) or C-B (N = 76). The primary end point was progression-free survival (PFS). The primary PFS analysis was performed after 100 events (radiological progression or death) were observed. Secondary end points included overall survival (OS), quality of life (QoL; QLQ-C30 and QLQ-CR29 questionnaires), and safety.

Results: Median (range) duration of treatment was 7.8 (6.0-9.7) months and 6.2 (4.1-9.1) months in the TT-B and C-B groups, respectively. Median (range) PFS was 9.2 (7.6-11.6) and 7.8 (5.5-10.1) months, respectively. Median (range) OS was 18 (15.2 to NA) and 16.2 (12.5 to NA) months, respectively. QoL questionnaires showed no relevant changes over time for either treatment. Therapies were well tolerated. Patients receiving TT-B had more grade ≥3 neutropenia (47% versus 5% with C-B). Patients receiving C-B had more grade ≥3 hand-foot syndrome (12% versus 0% with TT-B) and grade ≥3 diarrhea (8% versus 1% with TT-B), consistent with the known safety profiles of these agents.

Conclusion: TT-B treatment showed promising clinical activity in untreated patients with unresectable mCRC ineligible for intensive therapy, with an acceptable safety profile and no clinically relevant changes in QoL.

Clinical trial information: NCT02743221 (ClinicalTrials.gov).

Keywords: TASCO1 study; bevacizumab; capecitabine; intensive therapy; metastatic colorectal cancer; trifluridine/tipiracil.

Conflict of interest statement

Disclosure EVC has received research funding from Amgen, Bayer, Boehringer Ingelheim, Celgene, Ipsen, Lilly, Merck, Merck KgaA, Novartis, Roche, Sanofi, and Servier; and has attended advisory board for Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. ID has received research funding from AstraZeneca Pharma Poland, Bayer, Bristol-Myers Squibb, Celgene, Eli Lilly, Immutep, Janssen-Cilag, Merck, MorphoSys, Novartis, Regeneron Pharmaceuticals, Roche, Servier, Tesaro. MPS has attended advisory boards and chaired meeting for Roche, Merck, Servier, Amgen, Sanofi, and Eisai. PP has received research funding from Amgen, Celgene, Lilly, Merck KgaA, Roche, Taiho, Nordic drugs, and Servier. GA has received research funding from Servier and Bayer; has attended advisory boards for Servier, Bayer, Amgen, Sanofi, Merck Serono, Bristol-Myers Squibb, and Roche; and has received travel expense and accommodation from Servier, Bayer, Amgen, and Roche. CB has attended advisory boards for Roche, Servier, and Sanofi; and has received a research grant from Roche. RG-J has received research funding from Servier. CJAP has an advisory role for Servier. AJVdW, MF, DS, HK, and have received research funding from Servier. PG-A has attended advisory boards and chaired meeting for Roche, Merck, Amgen, Sanofi, Lilly, and Servier. HW has received honoraria, attended advisory boards, received travel grants and/or speaker for BMS, Lilly, Roche, Pfizer, Biotheranostics, Bayer, Servier, Merck-Serono KGaA, Sirtex Medical, Sanofi-Aventis, Celgene, Array; has received research funding from Sirtex Medical, Merck Serono, Pfizer, Merck; and charitable/grants from CRUK, MRC, BRC-Imperial, National Institute for Health Research (NIHR), and CUP Foundation. AF has received compensation for participation to Advisory Boards and Research Grants to his institution from Amgen, Bayer, Merck, MSD, Roche, Lilly, Servier, and Bristol Meyers Squibb. AK, AE, PA, and NA are employees of Servier. The views expressed in the submitted article are the authors' own and not an official position of the institution or funder.

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.