Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study.

BACKGROUND

In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment.

PATIENTS AND METHODS

In 14-day cycles, patients received FTD/TPI 35 mg/m

RESULTS

In total, 54 patients were enrolled: 37 in cohort A and 17 in cohort B. Recruitment in cohort B was stopped early due to the low response rate (RR) observed at interim analyses of efficacy. The most common adverse events (AEs) in cohort A were neutropenia/decreased neutrophils (75.7%), nausea (59.5%), vomiting (40.5%), diarrhoea (37.8%), peripheral sensory neuropathy (37.8%), fatigue (35.1%) and decreased appetite (35.1%). In cohort B, the most common AEs were neutropenia/decreased neutrophils (70.6%), diarrhoea (58.8%), nausea (47.1%), vomiting (47.1%), fatigue (47.1%), asthenia (41.2%), paraesthesia (41.2%), thrombocytopenia/decreased platelets (35.3%) and decreased appetite (35.3%). Confirmed objective RR was 17.1% in cohort A and 7.1% in cohort B; the corresponding values for median progression-free survival in the two cohorts were 6.3 and 6.0 months.

CONCLUSION

FTD/TPI plus oxaliplatin and bevacizumab or nivolumab had an acceptable safety profile and demonstrated antitumour activity in previously treated patients with mCRC.

Informations de copyright

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

Déclaration de conflit d'intérêts

Disclosure RB has received honoraria from Bayer, AstraZeneca, Sanofi, Novartis, Amgen, Hoffmann La Roche, Pfizer, Janssen-Cilag, Bristol Myers Squibb and Merck. AC has received consulting/advisory honoraria from Lilly, Amgen, Servier, BMS and Sanofi, and travel accommodation from Amgen, Servier and Merck. AH reports personal fees and nonfinancial support from Servier, during the conduct of the study; grants from Incyte; personal fees from Amgen, Lilly, Debiopharm, Incyte, Bayer, EISAI; grants and nonfinancial support from AstraZeneca; grants from Boehringer Ingelheim, Janssen-Cilag, Merck, Novartis, Pfizer, BMS and Sanofi. GR received honoraria from Novartis, Pfizer, Lilly, Amgen, Roche, SWIXX and Merck. MPS reports personal fees from Servier, Amgen and Merck. GP reports advisory role and speakers honorarium from Servier. AS reports grants and/or personal fees or consulting or advisory role, speakers bureau, research funding, travel/accommodations/expenses from Merck KGaA, Bristol-Myers Squibb, Amgen, Roche, MSD, Servier, Sanofi, AstraZeneca, Bayer, Lilly and Celgene. TA has served in a consulting/advisory role and/or received honoraria for Amgen, Bristol-Myers Squibb, Chugai, Clovis, Grindstone, GSK, HalioDx, MSD Oncology, Pierre Fabre, Roche/Ventana, Sanofi, Servier and Tesaro, and has received travel, accommodation and other expenses from Roche/Genentech/Ventana, MSD Oncology and Bristol-Myers Squibb. GA received honoraria for consulting/advisory roles from Amgen, Bristol-Myers Squibb, Merck Serono, Roche, Bayer, Servier and Sanofi; travel and accommodation expenses from Amgen, Roche, Servier, Bayer and Sanofi and has had an advisory role without compensation for Treos Bio Limited. JE has received honoraria from Servier, Eisai, MSD, BTG, BMS, Ipsen, Bayer and Roche. JT reports personal financial interest in the form of a scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Biocartis, Boehringer Ingelheim, Chugai, F. Hoffmann-La Roche Ltd., Foundation Medicine, Genentech Inc., Genmab A/S, HalioDx SAS, Halozyme, Imugene Ltd., Inflection Biosciences Ltd., Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, Roche Diagnostics, Sanofi, Seagen, Seattle Genetics, Servier, Symphogen, Taiho and VCN Biosciences. CL, NA, VC and RF are employees of Servier. All other authors have declared no conflicts of interest.