Evidence map›Paper›PMID 31868905›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2019

Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and first-line efficacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial.

S Stintzing, P Wirapati, H-J Lenz, D Neureiter, L Fischer von Weikersthal, T Decker, A Kiani, F Kaiser, S Al-Batran, T Heintges and 13 more

Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00433927 (Multicenter Randomized Trial Evaluating FOLFIRI Plus Cetuximab Versus FOLFIRI Plus Bevacizumab in First Line Treatment of Metastatic Colorectal Cancer.), which is not on this map. Cited by 134 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed, 1 pooled it
–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.

NCT00433927 phase3unknown statusnot on this map

Multicenter Randomized Trial Evaluating FOLFIRI Plus Cetuximab Versus FOLFIRI Plus Bevacizumab in First Line Treatment of Metastatic Colorectal Cancer.

TypeinterventionalSponsorPD Dr. med. Volker HeinemannRan2007 to 2016Enrolled568ConditionsNeoplasm Metastasis, Colorectal CancerArms5-FU, folinic acid, irinotecan, cetuximab, bevacizumab
3 · Its place in the literature

Who cites it

134 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  6. Impact of Consensus Molecular Subtype on Survival in Patients With Metastatic Colorectal Cancer: Results From CALGB/SWOG 80405 (Alliance).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019
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  12. BRAFJournal of experimental & clinical cancer research : CR · 2026
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74 more citing papers are in PubMed but not listed here.

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

23 authors.

S StintzingDepartment of Medicine, Division of Hematology, Oncology, and Tumor Immunology (CCM), Charité Universitaetsmedizin Berlin, Berlin, Germany. Electronic address: sebastian.stintzing@charite.de.
P WirapatiSIB Swiss Institute of Bioinformatics, Bioinformatic Core Facility, Lausanne, Switzerland.
H-J LenzUSC Norris Comprehensive Cancer Center, Los Angeles, USA.
D NeureiterInstitute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria.
L Fischer von WeikersthalGesundheitszentrum St. Marien, Amberg.
T DeckerOncological Practice, Ravensburg.
A KianiMedizinische Klinik IV, Klinikum Bayreuth, Bayreuth.
F KaiserVK&K Studien GbR, Landshut.
S Al-BatranDepartment of Hematology and Oncology, Krankenhaus Nordwest, Frankfurt/Main.
T HeintgesDepartment of Medicine II, Städtisches Klinikum Neuss, Neuss.
C LerchenmüllerOncological Practice, Münster.
C KahlHaematology and Oncology, Staedtisches Klinikum Magdeburg, Magdeburg.
G SeipeltOncological Practice, Bad Soden.
F KullmannDepartment of Medicine I, Klinikum Weiden, Weiden.
M MoehlerUniversity Hospital Mainz, Mainz, Germany.
W ScheithauerDepartment of Internal Medicine I & Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria.
S HeldClinAssess GmbH, Leverkusen.
D P ModestDepartment of Medicine III, University Hospital, LMU Munich, Munich.
A JungInstitute of Pathology University of Munich, Munich, Germany.
T KirchnerInstitute of Pathology University of Munich, Munich, Germany.
D AderkaDepartment of Gastrointestinal Oncology, Chaim Sheba Medical Center, Ramat Gan, Israel.
S TejparMolecular Digestive Oncology, UZ Leuven, Belgium.
V HeinemannDepartment of Medicine III, University Hospital, LMU Munich, Munich.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFIRE-3 compared first-line therapy with FOLFIRI plus either cetuximab or bevacizumab in 592 KRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. The consensus molecular subgroups (CMS) are grouping CRC samples according to their gene-signature in four different subtypes. Relevance of CMS for the treatment of mCRC has yet to be defined. PATIENTS AND

methodsIn this exploratory analysis, patients were grouped according to the previously published tumor CRC-CMSs. Objective response rates (ORR) were compared using chi-square test. Overall survival (OS) and progression-free survival (PFS) times were compared using Kaplan-Meier estimation, log-rank tests. Hazard ratios (HR) were estimated according to the Cox proportional hazard method.

resultsCMS classification could be determined in 438 out of 514 specimens available from the intent-to-treat (ITT) population (n = 592). Frequencies for the remaining 438 samples were as follows: CMS1 (14%), CMS2 (37%), CMS3 (15%), CMS4 (34%). For the 315 RAS wild-type tumors, frequencies were as follows: CMS1 (12%), CMS2 (41%), CMS3 (11%), CMS4 (34%). CMS distribution in right- versus (vs) left-sided primary tumors was as follows: CMS1 (27% versus 11%), CMS2 (28% versus 45%), CMS3 (10% versus 12%), CMS4 (35% versus 32%). Independent of the treatment, CMS was a strong prognostic factor for ORR (P = 0.051), PFS (P < 0.001), and OS (P < 0.001). Within the RAS wild-type population, OS observed in CMS4 significantly favored FOLFIRI cetuximab over FOLFIRI bevacizumab. In CMS3, OS showed a trend in favor of the cetuximab arm, while OS was comparable in CMS1 and CMS2, independent of targeted therapy.

conclusionsCMS classification is prognostic for mCRC. Prolonged OS induced by FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab in the FIRE-3 study appears to be driven by CMS3 and CMS4. CMS classification provides deeper insights into the biology to CRC, but at present time has no direct impact on clinical decision-making.The FIRE-3 (AIO KRK-0306) study had been registered at ClinicalTrials.gov: NCT00433927.

Indexed as

AgedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiomarkers, TumorCamptothecinCetuximabClinical Decision-MakingColonColorectal NeoplasmsDNA Mutational AnalysisFemaleFluorouracilGene Expression ProfilingHumansKaplan-Meier EstimateLeucovorinBevacizumabBiomarkers, TumorCamptothecinCetuximabFluorouracilLeucovorinbevacizumabcetuximabCMScolorectal cancer

Identifiers

PMID31868905
PMCPMC6927316

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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 OpenQuestion graph.