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Review
. 2024 Oct;25(10):1312-1322.
doi: 10.1007/s11864-024-01261-w. Epub 2024 Sep 26.

Clinical Trial Data Review of the Combination FTD/TPI + Bevacizumab in the Treatment Landscape of Unresectable Metastatic Colorectal Cancer

Thierry André  1 , Eric Van Cutsem  2 , Julien Taieb  3 , Marwan Fakih  4 , Gerald W Prager  5 , Fortunato Ciardiello  6 , Alfredo Falcone  7 , Mark Saunders  8 , Nadia Amellal  9 , Lucas Roby  9 , Josep Tabernero  10 , Per Pfeiffer  11
Affiliations
Review

Clinical Trial Data Review of the Combination FTD/TPI + Bevacizumab in the Treatment Landscape of Unresectable Metastatic Colorectal Cancer

Thierry André et al. Curr Treat Options Oncol. 2024 Oct.

Abstract

Recommended first and second line treatments for unresectable metastatic colorectal cancer (mCRC) include fluorouracil-based chemotherapy, anti-vascular endothelial growth factor (VEGF)-based therapy, and anti-epidermal growth factor receptor-targeted therapies. In third line, the SUNLIGHT trial showed that trifluridine/tipiracil + bevacizumab (FTD/TPI + BEV) provided significant survival benefits and as such is now a recommended third line regimen in patients with refractory mCRC, irrespective of RAS mutational status and previous anti-VEGF treatment. Some patients are not candidates for intensive combination chemotherapy as first-line therapy due to age, low tumor burden, performance status and/or comorbidities. Capecitabine (CAP) + BEV is recommended in these patients. In the SOLSTICE trial, FTD/TPI + BEV as a first line regimen in patients not eligible for intensive therapy was not superior to CAP + BEV in terms of progression-free survival (PFS). However, in SOLSTICE, FTD/TPI + BEV resulted in similar PFS, overall survival, and maintenance of quality of life as CAP + BEV, with a different safety profile. FTD/TPI + BEV offers a possible first line alternative in patients for whom CAP + BEV is an unsuitable treatment. This narrative review explores and summarizes the clinical trial data on FTD/TPI + BEV.

Keywords: Bevacizumab; Combination therapy; Efficacy; FTD/TPI; Metastatic colorectal cancer.

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Conflict of interest statement

Thierry André reports attending advisory board meetings and receiving consulting fees from Abbvie, Astellas, Aptitude Health, Bristol Myers Squibb, Gritstone Oncology, Gilead, GlaxoSmithKline, Merck & Co. Inc., Nordic Oncology, Seagen, Servier, Takeda and honoraria from Bristol Myers Squibb, GlaxoSmithKline, Merck & Co. Inc., Merck Serono, Roche, Sanofi, Seagen and Servier; and a DMC member role for Inspirna and support for meetings from Bristol Myers Squibb, Merck & Co. Inc. and Servier. Eric Van Cutsem participated in advisory boards for Abbvie, ALX, Amgen, Array, Astellas, Astrazeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Takeda, Terumo, Taiho, Zymeworks and received research grants from Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier paid to his institution. Julien Taieb has received fees for advisory/consultancy roles from Lilly, MSD, Amgen, Merck Serono, Novartis, Roche, Sanofi, Servier, HalioDX SAS and Pierre Fabre. Marwan Fakih has received honoraria from Amgen, has received fees for speaker, consultancy or advisory roles from Amgen, Array BioPharma, Bayer, Guardant360 and Pfizer, and has received research grant support from Amgen, Novartis and AstraZeneca. Gerald Prager has provided consulting/advisory for Amgen, Daiichi Sanyo Europe GmbH, Incyte, Merck Serono, Pierre Fabre, Roche/Genetech, Servier, Lilly O., AstraZeneca, Arcus Bioscience, and Bayer US LLC Fortunato Ciardiello has provided consulting/advisory for Amgen, Merck KGaA, Pfizer, Roche/Genentech, Bayer US, LLC; and received research funding from Amgen, BMS, Ipsen, Merck KGaA, Merck Sharp & Dome, Roche/Genetech, Servier, Symphogen; Bayer US, LLC. Alfredo Falcone: reports no conflict of interest. Mark Saunders reports advisory role or speaking for Takeda, Bayer, GSK, MSD and Servier. Nadia Amellal and Lucas Roby are employees of Servier. Joseph Tabernero has provided consulting/advisory for Alentis Therapeutics, Amgen, AstraZeneca, Aveo Oncology, Boehringer Ingelheim, Cardiff Oncology, CARSgen Therapeutics, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, hC Bioscience, Immodulon Therapeutics, Inspirna Inc, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Takeda Oncology and Tolremo Therapeutics. Stocks: Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology and 1TRIALSP. Educational collaboration: Medscape Education, PeerView Institute for Medical Education and Physicians Education Resource (PER). Per Pfeiffer reports advisory role or speaking for Servier.

Figures

Fig. 1
Fig. 1
Median overall survival in subgroups in the SUNLIGHT trial [23, 26]. Abbreviations: BEV, bevacizumab; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; FTD/TPI, trifluridine/tipiracil; HR, hazard ratio; VEGF, vascular endothelial growth factor
Fig. 2
Fig. 2
Change from baseline of (A) global health status (EORTC QLQ-C30), and (B) general QoL (EQ-5D-5L), in the SUNLIGHT trial [29]. Abbreviations: BEV, bevacizumab; EORTC QLQ-C30, The European Organisation for Research and Treatment of Cancer Quality of Life. Questionnaire—Core Questionnaire; EQ-5D-5L, EuroQol 5 Dimension 5 Level; FTD/TPI, trifluridine/tipiracil; QoL, quality of life; SD, standard deviation
Fig. 3
Fig. 3
Median progression-free survival in SOLSTICE subgroups [19]. Abbreviations: BEV, bevacizumab; CAP, capecitabine; CI, confidence interval; FTD/TPI, trifluridine/tipiracil; HR, hazard ratio
See this image and copyright information in PMC

References

    1. Cervantes A, Adam R, Rosello S, Arnold D, Normanno N, Taieb J, et al. Metastatic colorectal cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(1):10–32. 10.1016/j.annonc.2022.10.003. - PubMed
    1. Benson AB, Venook AP, Adam M, Change G, Chen YJ, Ciombor KK, et al. Colon cancer, Version 3.2024, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2024;22:e240029. 10.6004/jnccn.2024.0029. - PubMed
    1. Seymour MT, Thompson LC, Wasan HS, Middleton G, Brewster AE, Shepherd SF, et al. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet. 2011;377(9779):1749–59. 10.1016/S0140-6736(11)60399-1. - PMC - PubMed
    1. Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14(11):1077–85. 10.1016/S1470-2045(13)70154-2. - PubMed
    1. Arnold D, Prager GW, Quintela A, Stein A, Moreno Vera S, Mounedji N, et al. Beyond second-line therapy in patients with metastatic colorectal cancer: a systematic review. Ann Oncol. 2018;29(4):835–56. 10.1093/annonc/mdy038. - PMC - PubMed

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