Evidence map›Paper›PMID 36455506›Full record

ArticleESMO open2022

Targeting the FGF/FGFR axis and its co-alteration allies.

Y Uehara, S Ikeda, K H Kim, H J Lim, J J Adashek, H E Persha, R Okamura, S Lee, J K Sicklick, S Kato and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ESMO open, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

21 citing papers in PubMed, 27 citations in OpenAlex.

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  12. Receptor Tyrosine Kinase Signaling InvolvesTropical medicine and infectious disease · 2024
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  18. Elacestrant plus alpelisib in anTherapeutic advances in medical oncology · 2024
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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

11 authors at 6 institutions in 3 countries.

Y UeharaDepartment of Precision Cancer Medicine, Center for Innovative Cancer Treatment, Tokyo Medical and Dental University, Tokyo; Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
S IkedaDepartment of Precision Cancer Medicine, Center for Innovative Cancer Treatment, Tokyo Medical and Dental University, Tokyo; Center for Personalized Cancer Therapy, Division of Hematology/Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, USA.
K H KimCenter for Personalized Cancer Therapy, Division of Hematology/Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, USA; Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul.
H J LimCenter for Personalized Cancer Therapy, Division of Hematology/Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, USA; Department of Internal Medicine, Veterans Health Service Medical Center, Seoul, Republic of Korea.
J J AdashekDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore.
H E PershaPurdue University College of Pharmacy, Purdue University, West Lafayette, USA.
R OkamuraCenter for Personalized Cancer Therapy, Division of Hematology/Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, USA; Department of Surgery, Kyoto University Hospital, Kyoto, Japan.
S LeeCenter for Personalized Cancer Therapy, Division of Hematology/Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, USA.
J K SicklickCenter for Personalized Cancer Therapy and Division of Surgical Oncology, Department of Surgery, UC San Diego Moores Cancer Center, La Jolla, USA.
S KatoCenter for Personalized Cancer Therapy, Division of Hematology/Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, USA. Electronic address: smkato@health.ucsd.edu.
R KurzrockWIN Consortium for Personalized Cancer Therapy, Paris, France; Medical College of Wisconsin Cancer Center and Genome Science and Precision Medicine Center, Milwaukee, USA; University of Nebraska (adjunct), Lincoln, Nebraska.
University of California San Diego · USJohns Hopkins Hospital · USMoores Cancer CenterPurdue University West Lafayette · USTokyo Medical and Dental University · JPUniversity of Nebraska–Lincoln · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWe analyzed the FGF/FGFR and co-alteration cancer landscape, hypothesizing that combination therapy might be useful in the presence of co-drivers. MATERIALS AND

methodsWe describe FGF/FGFR-altered pathways, prognosis, and co-alterations [cBioPortal (N = 7574)] and therapeutic outcomes [University of California San Diego Molecular Tumor Board (MTB) (N = 16)].

resultsPatients whose cancers harbored FGF/FGFR alterations (N = 1074) versus those without them (N = 6500) had shorter overall survival (OS) (median: 23.1 versus 26.4 months, P = 0.038) (cBioPortal). Only 6.1% (65/1074 patients) had no pathogenic co-alterations accompanying FGF/FGFR axis abnormalities. The most frequently co-altered pathways/genes involved: TP53 (70%); cell cycle (58%); PI3K (55%); and receptor tyrosine kinases and mitogen-activated protein kinase (MAPK) (65%). Harboring alterations in both FGF/FGFR and in the TP53 pathway or in the cell cycle pathway correlated with shorter OS (versus FGF/FGFR-altered without those co-altered signals) (P = 0.0001 and 0.0065). Four of 16 fibroblast growth factor receptor (FGFR) inhibitor-treated patients presented at MTB attained durable partial responses (PRs) (9, 12, 22+, and 52+ months); an additional two, stable disease (SD) of ≥6 months (13+ and 15 months) [clinical benefit rate (SD ≥ 6 months/PR) = 38%]. Importantly, six patients with cyclin pathway co-alterations received the CDK4/6 inhibitor palbociclib (75 mg p.o. 3 weeks on, 1 week off) and the multikinase FGFR inhibitor lenvatinib (10 mg p.o. daily); three (50%) achieved a PR [9 (ovarian), 12 (biliary), and 52+ months (osteosarcoma)]. Palbociclib and lenvatinib were tolerated well.

conclusionsFGF/FGFR alterations portend a poor prognosis and are frequently accompanied by pathogenic co-aberrations. Malignancies harboring co-alterations that activate both cyclin and FGFR pathways can be co-targeted by CDK4/6 and FGFR inhibitors.

Indexed as

NeoplasmsQuinolinesFibroblast Growth FactorsHumansPhenylurea CompoundsReceptors, Fibroblast Growth FactorFibroblast Growth FactorslenvatinibPhenylurea CompoundsQuinolinesReceptors, Fibroblast Growth Factorcombination therapydrug resistanceFGFRmatched therapyprecision cancer medicinetyrosine kinase inhibitor

Identifiers

PMID36455506
PMCPMC9808461
OpenAlexW4310366636

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.