Evidence map›Paper›PMID 34364385›Full record

Trial reportBMC cancer2021

Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib vs everolimus in advanced renal cell carcinoma.

Thomas Powles, Toni K Choueiri, Robert J Motzer, Eric Jonasch, Sumanta Pal, Nizar M Tannir, Sabina Signoretti, Rajesh Kaldate, Christian Scheffold, Evelyn Wang and 3 more

Erratum issued Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01865747 (A Phase 3, Randomized, Controlled Study of Cabozantinib), which is not on this map. Cited by 15 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 2 pooled it
1.9field-weighted citation impact, top 13% of its field
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.

NCT01865747 phase3completednot on this map

A Phase 3, Randomized, Controlled Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma That Has Progressed After Prior VEGFR Tyrosine Kinase Inhibitor Therapy

TypeinterventionalSponsorExelixisRan2013 to 2021Enrolled658ConditionsRenal Cell CarcinomaArmsCabozantinib tablets, Everolimus (Afinitor) tablets
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.

  1. Pooled it
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  6. Review
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  14. Immune cell mediated cabozantinib resistance for patients with renal cell carcinoma.Integrative biology : quantitative biosciences from nano to macro · 2021
    Article
  15. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 9 institutions in 3 countries.

Thomas PowlesBarts Cancer Institute, Queen Mary University of London, London, UK. thomas.powles1@nhs.net.
Toni K ChoueiriDana-Farber Cancer Center, Boston, MA, USA.
Robert J MotzerMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Eric JonaschUniversity of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sumanta PalCity of Hope National Medical Center, Duarte, CA, USA.
Nizar M TannirUniversity of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sabina SignorettiBrigham and Women's Hospital, Boston, MA, USA.
Rajesh Kaldate *Exelixis, Inc, Alameda, CA, USA.
Christian ScheffoldExelixis, Inc, Alameda, CA, USA.
Evelyn Wang *Exelixis, Inc, Alameda, CA, USA.
Dana T AftabExelixis, Inc, Alameda, CA, USA.
Bernard EscudierGustave-Roussy, Villejuif, France.
Daniel J GeorgeDuke Cancer Institute, Durham, NC, USA.
Exelixis (United States) · USThe University of Texas MD Anderson Cancer Center · USBrigham and Women's Hospital · USCity Of Hope National Medical Center · USDana-Farber Cancer Institute · USDuke Cancer InstituteInstitut Gustave Roussy · FRMemorial Sloan Kettering Cancer Center · USQueen Mary University of London · GB

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundIn the phase 3 METEOR trial, cabozantinib improved progression-free survival (PFS) and overall survival (OS) versus everolimus in patients with advanced RCC after prior antiangiogenic therapy.

methodsIn this exploratory analysis, plasma biomarkers from baseline and week 4 from 621 of 658 randomized patients were analyzed for CA9, HGF, MET, GAS6, AXL, VEGF, VEGFR2, and IL-8. PFS and OS were analyzed by baseline biomarker levels as both dichotomized and continuous variables using univariate and multivariable methods. For on-treatment changes, PFS and OS were analyzed using fold change in biomarker levels at week 4. Biomarkers were considered prognostic if p < 0.05 and predictive if p

resultsHazard ratios for PFS and OS favored cabozantinib versus everolimus for both low and high baseline levels of all biomarkers (hazard ratios ≤0.78). In univariate analyses, low baseline HGF, AXL, and VEGF were prognostic for improvements in both PFS and OS with cabozantinib, and low HGF was prognostic for improvements in both PFS and OS with everolimus. Low AXL was predictive of relative improvement in PFS for cabozantinib versus everolimus. Results were generally consistent when baseline biomarkers were expressed as continuous variables, although none were predictive of benefit with treatment. In multivariable analysis, low baseline HGF was independently prognostic for improved PFS for both cabozantinib and everolimus; low HGF, GAS6, and VEGF were independently prognostic for improved OS with cabozantinib. No biomarkers were independently prognostic for OS with everolimus. On-treatment increases in some biomarkers appeared prognostic for PFS or OS with cabozantinib in univariate analyses; however, none were independently prognostic in multivariable analysis.

conclusionsPFS and OS were improved with cabozantinib versus everolimus at high and low baseline levels of all biomarkers. Low baseline HGF was consistently identified as a prognostic biomarker for improved PFS or OS with cabozantinib or everolimus, supporting further prospective evaluation of the prognostic significance of HGF in advanced RCC.

trial registrationClinicalTrials.gov NCT01865747 (registered on 05/31/2013).

Indexed as

AnilidesBiomarkers, TumorCarcinoma, Renal CellEverolimusHumansKaplan-Meier EstimateKidney NeoplasmsPrognosisPyridinesRetreatmentTreatment OutcomeAnilidesBiomarkers, TumorcabozantinibEverolimusPyridinesBiomarkerCabozantinibEverolimusMETEORRenal cell carcinoma

Identifiers

PMID34364385
PMCPMC8349489
OpenAlexW3187533975

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.