Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Nov;27(11):4203-4213.
doi: 10.1007/s12094-025-03907-z. Epub 2025 May 8.

Predictive factors of efficacy for FTD/TPI plus bevacizumab in refractory metastatic colorectal cancer patients: a subanalysis of the Spanish cohort from the SUNLIGHT phase III trial

Gemma Soler  1 , Cristina Grávalos  2 , Fernando Rivera  3 , María José Safont  4 , Anna C Virgili  5 , Manuel Valladares-Ayerbes  6 , Reyes Ferreiro-Monteagudo  7 , María José Ortiz-Morales  8 , Eduardo Polo-Marques  9 , Irina Kornusova-Bersheva  10 , Elsa Soustre  10 , Weiyu Yao  11 , Elena Élez  12
Affiliations
Clinical Trial

Predictive factors of efficacy for FTD/TPI plus bevacizumab in refractory metastatic colorectal cancer patients: a subanalysis of the Spanish cohort from the SUNLIGHT phase III trial

Gemma Soler et al. Clin Transl Oncol. 2025 Nov.

Abstract

Background: The addition of bevacizumab to trifluridine-tipiracil (FTD/TPI) therapy improves outcomes in patients with refractory metastatic colorectal cancer (CRC). However, predictive factors of efficacy for FTD/TPI when used in combination with bevacizumab are not yet fully recognized.

Methods: Patients included in the Spanish cohort of the SUNLIGHT trial were evaluated. The primary endpoint of this post-hoc exploratory subanalysis was overall survival (OS). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), safety and the assessment of potential predictive factors of efficacy for FTD/TPI plus bevacizumab, such as age, KRAS mutational status, the incidence of neutropenia, patient prognosis, and prior administration of bevacizumab.

Results: A total of 115 patients were analysed, 58 receiving FTD/TPI and 57 FTD/TPI plus bevacizumab. The median OS was 8.5 vs. 10.6 months (p = 0.254), respectively, and the median PFS was 2.4 vs. 4.7 months (p < 0.0001), respectively. Severe neutropenia affected 20% more patients in the experimental arm than in the control arm (51% vs. 31%, respectively). The univariate analysis showed that a benefit of adding bevacizumab to FTD/TPI in terms of PFS was observed in all previously defined patient subgroups and was accompanied by DCR of 69% for FTD/TPI plus bevacizumab vs. 45% in arm of FTD/TPI alone.

Conclusions: The addition of bevacizumab to FTD/TPI tends to improve OS probably due to the reduced number of patients included in this cohort and significantly improved PFS in all patient subgroups with metastatic CRC. Prospective studies are needed to confirm these results and to find out additional predictive factors that help us to discriminate which patients would benefit most from FTD/TPI plus bevacizumab.

Keywords: Aging; Digestive tumours; Prognosis; Targeted therapies; Vascular endothelial growth factors.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: Gemma Soler has no conflicts of interest. Cristina Grávalos has no conflicts of interest. Fernando Rivera has received advisory/consultancy fees from Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Lilly, Merck KGaA, Merck Sharp & Dohme, Organon, Hoffmann-La Roche, Sanofi, and Servier; speaker engagements from Amgen, Bayer, Bristol Myers Squibb, Celgene, Lilly, Merck KGaA, Merck Sharp & Dohme, Hoffmann-La Roche, Sanofi, and Servier; research funding from Amgen, Bayer, Celgene, Lilly, Merck KGaA, Merck Sharp & Dohme, Hoffmann-La Roche, Sanofi, and Servier; and grants and other fundings from Amgen, Bristol Myers Squibb, and Merck Sharp & Dohme. María José Safont has received advisory/consultancy fees from Amgen, Bayer, Bristol Myers Squibb, Merck KGaA, Merck Sharp & Dohme, Pierre Fabre, Pfizer, and Servier; and speaker engagements from Amgen, Bristol Myers Squibb, Lilly, Merck KGaA, Merck Sharp & Dohme, Servier, and Takeda. Anna C. Virgili has received advisory/consultancy fees from Merck KGaA, and Pierre Fabre; and travel grants from Amgen, Merck KGaA, and Merck Sharp & Dohme. Manuel Valladares-Ayerbes has received advisory/consultancy fees from Amgen, Sanofi, and Servier; speaker engagements from Bristol Myers Squibb, Merck KGaA, and Merck Sharp & Dohme; grants and other fundings from Amgen, Merck KGaA, Hoffmann-La Roche, and Servier. Reyes Ferreiro-Monteagudo has received advisory/consultancy fees from Amgen; speaker engagements from Amgen, Merck KGaA, Merck Sharp & Dohme, Servier and Takeda. María Jose Ortiz-Morales has no conflicts of interest. Eduardo Polo-Marqués has received advisory/consultancy fees from Amgen, Leo Pharma, Merck KGaA, Novartis, Pierre-Fabre, and Servier. Irina Kornusova-Bersheva is an employee of Laboratorios Servier in Spain. Elsa Soustre is an employee of Laboratorios Servier in Spain. Weiyu Yao is an employee of Servier Pharmaceuticals in Boston, MA, USA. Elena Élez has received advisory/consultancy fees from Agenus, Amgen, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, CureTeq AG, GlaxoSmithKline, Hoffmann-La Roche, Janssen Cilag, Johnson & Johnson, Lilly, Medscape, Merck KGaA, Merck Sharp & Dohme, Novartis, Organon, Pfizer, Pierre Fabre, Repare Therapeutics Inc., RIN Institute Inc., Rottapharm Biotech, Sanofi, Seagen International GmbH, Servier, and Takeda; speaker engagements from Agenus, Amgen, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, CureTeq AG, GlaxoSmithKline, Hoffmann-La Roche,, Janssen Cilag, Johnson & Johnson, Lilly, Medscape, Merck KGaA, Merck Sharp & Dohme, Novartis, Organon, Pfizer, Pierre Fabre, Repare Therapeutics Inc., RIN Institute Inc., Rottapharm Biotech, Sanofi, Seagen International GmbH, Servier, and Takeda; and grants and institutional grants and other fundings from Abbvie, Agenus, Amgen, Array Biopharma, AstraZeneca, Bayer, BeiGene, Bioncotech, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Debiopharm International SA, Enterome BioScience, Exelixis, Genentech, Gercor, GlaxoSmithKline, HalioDX SAS, Hoffmann-La Roche, Hutchinson Medipharma, Iovance Biotherapeutics, Janssen Cilag, MedImmune, Menarini, Merck KGaA, Merck Sharp & Dohme, Merus NV, Mirati, Nouscom, Novartis, Pfizer, NuCana plc., PharmaMar, Pledpharma AB, Redx Pharma PLC, Sanofi, Scandion Oncology, Seattle Genetics Inc., Servier, Sotio, Taiho Pharma, and Wntresearch AB. Ethics approval: The study has been performed in accordance with the ethical standards of the Declaration of Helsinki and its later amendments. Human and animal rights: This article does not contain any studies directly involving human participants, as it is a review of data already collected in a hernia database. Consent for publication: Not applicable.

References

    1. Morris VK, Kennedy EB, Baxter NN, Benson AB 3rd, Cercek A, Cho M, et al. Treatment of metastatic colorectal cancer: ASCO guideline. J Clin Oncol. 2023;41(3):678–700. https://doi.org/10.1200/jco.22.01690 . - DOI - PubMed
    1. Pinheiro M, Moreira DN, Ghidini M. Colon and rectal cancer: an emergent public health problem. World J Gastroenterol. 2024;30(7):644–51. https://doi.org/10.3748/wjg.v30.i7.644 . - DOI - PubMed - PMC
    1. Saraiva MR, Rosa I, Claro I. Early-onset colorectal cancer: a review of current knowledge. World J Gastroenterol. 2023;29(8):1289–303. https://doi.org/10.3748/wjg.v29.i8.1289 . - DOI - PubMed - PMC
    1. Constantinou V, Constantinou C. Focusing on colorectal cancer in young adults (Review). Mol Clin Oncol. 2024;20(1):8. https://doi.org/10.3892/mco.2023.2706 . - DOI - PubMed
    1. Ohishi T, Kaneko MK, Yoshida Y, Takashima A, Kato Y, Kawada M. Current targeted therapy for metastatic colorectal cancer. Int J Mol Sci. 2023. https://doi.org/10.3390/ijms24021702 . - DOI - PubMed - PMC

Publication types

MeSH terms

LinkOut - more resources