Evidence map›Paper›PMID 41530374›Full record

ArticleNPJ precision oncology2026

Exploratory biomarker analysis of RAS/BRAF somatic mutations and gene expression signatures for predicting treatment effects of aflibercept in the velour trial.

Ting Pu, Allyson M Peddle, Pratyaksha Wirapati, Petros Tsantoulis, Qian Wu, Yourae Hong, Leslie Samuel, Jayesh Desai, Maigo Riener, Zacharenia Saridaki and 2 more

Registry-linked trialAbstract read
In one paragraph

Article in NPJ precision oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00561470 (A Multinational, Randomized, Double-blind Study, Comparing the Efficacy of Aflibercept Once Every 2 Weeks Versus Placebo in Patients With Metastatic Colorectal Cancer), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00561470 phase3completednot on this map

A Multinational, Randomized, Double-blind Study, Comparing the Efficacy of Aflibercept Once Every 2 Weeks Versus Placebo in Patients With Metastatic Colorectal Cancer (MCRC) Treated With Irinotecan / 5-FU Combination (FOLFIRI) After Failure of an Oxaliplatin Based Regimen

TypeinterventionalSponsorSanofiRan2007 to 2012Enrolled1,226ConditionsColorectal Neoplasms, Neoplasm MetastasisArmsPlacebo, Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®), FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin)
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Ting Pu *Digestive Oncology, KU Leuven, Belgium.
Allyson M Peddle *Digestive Oncology, KU Leuven, Belgium.
Pratyaksha WirapatiSwiss Institute of Bioinformatics, Lausanne, Switzerland.
Petros TsantoulisGeneva University Hospitals, Geneva, Switzerland.
Qian WuDigestive Oncology, KU Leuven, Belgium.
Yourae HongDigestive Oncology, KU Leuven, Belgium.
Leslie SamuelOncology Department, School of Medicine, Medical Sciences and Nutrition, Aberdeen Royal Infirmary, University of Aberdeen, Aberdeen, UK.
Jayesh DesaiPeter MacCallum Cancer Centre, Melbourne, Australia.
Maigo RienerDocrates Syöpäsairaala, Helsinki, Finland.
Zacharenia SaridakiFirst Oncology Department, Metropolitan Hospital, Piraeus, Greece.
David CunninghamThe Royal Marsden Hospital, London, UK.
Sabine TejparDigestive Oncology, KU Leuven, Belgium. sabine.tejpar@uzleuven.be.

Funding

Chinese Scholarship Council 202206380034Fonds Wetenschappelijk Onderzoek 1SF0424N
6 · The paper itself

Abstract

The phase III VELOUR trial demonstrated improved outcomes with aflibercept plus FOLFIRI in patients with metastatic colorectal cancer previously treated with oxaliplatin-based regimens. We retrospectively evaluated the prognostic and predictive impact of RAS/BRAF mutations, intrinsic consensus molecular subtype (iCMS), and tumour sidedness in 439 profiled patients. Targeted sequencing identified RAS mutations in 57.5% and BRAF mutations in 10.0% of evaluable tumours; 34.2% of tumours with complete genotyping were RAS/BRAF wild-type. Transcriptomic profiling classified 66.5% of tumours as iCMS2 and 33.5% as iCMS3. RAS/BRAF wild-type tumours showed numerically improved overall survival (OS) and progression-free survival (PFS) with aflibercept, whereas no clear benefit was observed in RAS-mutant tumours. iCMS subtyping was strongly prognostic, with iCMS2 patients demonstrating longer OS and PFS than iCMS3 (OS HR 0.57, 95%CI 0.45-0.72; PFS HR 0.70, 95%CI 0.56-0.88). Exploratory integrated analyses suggested OS benefit in RAS/BRAF wild-type iCMS2 tumours (HR 0.56, 95%CI 0.33-0.96) and a significant PFS advantage in bevacizumab-pretreated iCMS3 tumours (HR 0.41, 95%CI 0.20-0.85, q = 0.032). Right-sided tumours were associated with poorer OS, but no significant treatment interaction was observed. These findings support integrating genomic and transcriptomic biomarkers to refine patient selection for anti-VEGF therapy, warranting validation in prospective studies. ClinicalTrials.gov number: NCT00561470, registered 15 November 2007.

Identifiers

PMID41530374
PMCPMC12858838

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.