Evidence map›Paper›PMID 36502778›Full record

Trial reportESMO open2022

A phase II study to explore biomarkers for the use of mFOLFOX6/XELOX plus bevacizumab as a first-line chemotherapy in patients with metastatic colorectal cancer (WJOG7612GTR).

W Okamoto, K Sakai, A Makiyama, Y Yamamoto, K Shitara, T Denda, N Izawa, Y Nakano, T Nishina, T Esaki and 9 more

Open access · goldAbstract readClinical Trial, Phase II
In one paragraph

Trial report in ESMO open, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 47% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.

  1. Pooled it
  2. 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

19 authors at 10 institutions in 2 countries.

W OkamotoDepartment of Medical Oncology, Kindai University Faculty of Medicine, Osakasayama; Translational Research Support Section, National Cancer Center Hospital East, Kashiwa; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa; Cancer Treatment Center, Hiroshima University Hospital, Hiroshima.
K SakaiDepartment of Genome Biology, Kindai University Faculty of Medicine, Osakasayama.
A MakiyamaDepartment of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, Kitakyushu; Cancer Center, Gifu University Hospital, Gifu.
Y YamamotoDepartment of Gastroenterology, University of Tsukuba Hospital, Tsukuba.
K ShitaraDepartment of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa; Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya.
T DendaDivision of Gastroenterology, Chiba Cancer Center, Chiba.
N IzawaDepartment of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki.
Y NakanoDepartment of Medical Oncology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya.
T NishinaDepartment of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama.
T EsakiDepartment of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka.
H HaraDepartment of Gastroenterology, Saitama Cancer Center, Kitaadachi-gun.
Y MiuraDepartment of Medical Oncology, Toranomon Hospital, Minato-ku.
N BokuDepartment of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo.
K YamazakiDivision of Gastrointestinal Oncology, Shizuoka Cancer Center, Sunto-gun.
S HironakaDepartment of Medical Oncology and Hematology, Oita University Faculty of Medicine, Yufu.
T MisumiDepartment of Biostatistics, Yokohama City University School of Medicine, Yokohama.
I HyodoDepartment of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama.
K MuroDepartment of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
K NishioDepartment of Genome Biology, Kindai University Faculty of Medicine, Osakasayama. Electronic address: knishio@med.kindai.ac.jp.
Shikoku Cancer Center · JPAichi Cancer Center · JPChiba Cancer Center · JPNational Cancer Center · USNational Hospital Organization Kyushu Cancer Center · JPOita University · JPShizuoka Cancer Center · JPSt. Marianna University School of Medicine · JPUniversity of Tsukuba Hospital · JPYokohama City University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe purpose of this prospective study was to assess the ability of plasma vascular endothelial growth factor-A short isoforms (pVEGF-Asi) to predict bevacizumab (BV) efficacy and to explore other circulating biomarkers in metastatic colorectal cancer (mCRC) patients treated with modified FOLFOX6/XELOX plus BV (mFOLFOX6/XELOX + BV). PATIENTS AND

methodsPre-treatment plasma samples were collected from 100 mCRC patients receiving first-line chemotherapy with mFOLFOX6/XELOX + BV. The plasma levels of 11 angiogenesis-associated molecules, including pVEGF-Asi and 22 cancer-associated gene mutations in circulating tumor DNA, were analyzed. For the primary endpoint, we assumed that the hazard ratio (HR) for progression-free survival (PFS) calculated using a Cox proportional hazards model was <1.15, comparing patients with a high versus those with a low pVEGF-Asi level divided according to the median pVEGF-Asi value.

resultsThe median value of pVEGF-Asi was 37 (range 6.5-262) pg/ml. The HR for PFS between the high and low pVEGF-Asi patient groups was 1.3 [95% confidence interval (CI) 0.8-2.1; log rank, P = 0.25], which was larger than the predefined threshold of 1.15. The multivariate analysis demonstrated that PFS was significantly associated with plasma intercellular adhesion molecule-1 (pICAM-1) (≥190.0 versus <190.0 ng/ml; HR 2.1; 95% CI 1.3-3.5), RAS (mutant versus wild; HR 2.5; 95% CI 1.5-4.3), and FBXW7 (mutant versus wild; HR 2.8; 95% CI 1.2-6.8), whereas overall survival was significantly associated with pICAM-1 (HR 2.0; 95% CI 1.1-3.7) and RAS (HR 2.6; 95% CI 1.5-4.6).

conclusionsThe addition of BV was unable to compensate for the poor PFS associated with a high pVEGF-Asi level, suggesting that pVEGF-Asi is unlikely to be a good predictive biomarker of the efficacy of mFOLFOX6/XELOX + BV therapy. The clinical significance of circulating ICAM-1, mutant RAS, and mutant FBXW7 levels should be studied further.

Indexed as

Colonic NeoplasmsColorectal NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiomarkersCapecitabineDisease-Free SurvivalF-Box-WD Repeat-Containing Protein 7FluorouracilHumansOxaloacetatesProspective StudiesVascular Endothelial Growth Factor ABevacizumabBiomarkersCapecitabineF-Box-WD Repeat-Containing Protein 7FluorouracilOxaloacetatesVascular Endothelial Growth Factor Acirculating biomarkersmetastatic colorectal cancerpICAM-1 levelpVEGF-A short isoformsRAS and FBXW7 mutation

Identifiers

PMID36502778
PMCPMC9808456
OpenAlexW4311089005

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.