Evidence map›Paper›PMID 35171350›Full record

Trial reportCancer chemotherapy and pharmacology2022

Cabozantinib with or without Panitumumab for RAS wild-type metastatic colorectal cancer: impact of MET amplification on clinical outcomes and circulating biomarkers.

Jingquan Jia, Lauren Howard, Yingmiao Liu, Mark D Starr, John C Brady, Donna Niedzwiecki, John H Strickler, Andrew B Nixon

Registry-linked trialAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Publisher
In one paragraph

Trial report in Cancer chemotherapy and pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02008383 (Cabozantinib), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 27% 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.

NCT02008383 phase1completednot on this map

Cabozantinib (XL184) With Panitumumab in Subjects With KRAS Wild-Type Metastatic Colorectal Cancer and Cabozantinib Monotherapy in Subjects With MET Amplified Treatment-Refractory Colorectal Cancer

TypeinterventionalSponsorJohn Strickler, M.D.Ran2014 to 2018Enrolled29ConditionsColorectal CancerArmsPanitumumab, Cabozantinib
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025
    Review
  6. 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

8 authors at 2 institutions in 1 country.

Jingquan JiaDuke Cancer Institute, Durham, NC, USA.
Lauren HowardDuke Department of Biostatistics and Bioinformatics, Durham, NC, USA.
Yingmiao LiuDepartment of Medicine, Duke University Medical Center, Durham, NC, USA.
Mark D StarrDepartment of Medicine, Duke University Medical Center, Durham, NC, USA.
John C BradyDepartment of Medicine, Duke University Medical Center, Durham, NC, USA.
Donna NiedzwieckiDuke Department of Biostatistics and Bioinformatics, Durham, NC, USA.
John H StricklerDuke Cancer Institute, Durham, NC, USA.
Andrew B NixonDuke Cancer Institute, Durham, NC, USA. Andrew.nixon@duke.edu.ORCID 0000-0003-3971-2964
Duke Medical Center · USDuke University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeAcquired resistance to EGFR inhibitors in metastatic colorectal cancer (mCRC) remains a hurdle for effective treatment. MET amplification has been indicated as a driver of acquired resistance. Clinical activity has been demonstrated for the combination of EGFR and MET inhibitors in mCRC. But the impact of this regimen on angiogenesis and inflammation remains largely unknown.

methodsIn this non-randomized, open-label phase Ib/II study, four patients were treated with cabozantinib alone and 25 patients received the combination of cabozantinib and panitumumab. MET amplification was detected in blood in all four patients treated with cabozantinib monotherapy and 5/25 patients treated with cabozantinib and panitumumab combination therapy. Plasma samples from 28 patients were available for biomarker analysis.

resultsA panel of circulating protein biomarkers was assessed in patient plasma at baseline and on-treatment. Baseline marker levels were analyzed for prognostic value for clinical outcomes, including MET amplification as a covariate. HGF and OPN were prognostic for both progression-free survival (PFS) and overall survival (OS), while six markers (IL-6, VCAM-1, VEGF-R1, TSP-2, TIMP-1, ICAM-1) were prognostic only for OS. In patients with MET amplification, baseline PDGF-AA, PDGF-BB, TGF-β1, and VEGF-C levels were significantly higher, whereas baseline TGFβ-R3 levels were significantly lower than MET non-amplified patients. On-treatment change of four markers (CD73, PlGF, PDGF-BB, VEGF) were significantly different between MET amplified and non-amplified subpopulations.

conclusionThis study identified circulating HGF and several inflammatory and angiogenic proteins as prognostic biomarkers. Furthermore, MET amplification status is associated with both baseline expression and on-treatment modulation of members of angiogenesis and TGF-β pathway proteins. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02008383.

Indexed as

Colonic NeoplasmsColorectal NeoplasmsRectal NeoplasmsAnilidesBecaplerminBiomarkersErbB ReceptorsHumansPanitumumabPyridinesVascular Endothelial Growth Factor AAnilidesBecaplerminBiomarkerscabozantinibErbB ReceptorsPanitumumabPyridinesVascular Endothelial Growth Factor ACabozantinibMetastatic colorectal cancerPanitumumabPhase II clinical trialPrognostic biomarker

Identifiers

PMID35171350
OpenAlexW4213385724

What OpenQuestion holds

Textmetadata
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.