Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2014
Correlation of somatic mutations and clinical outcome in melanoma patients treated with Carboplatin, Paclitaxel, and sorafenib.
Open access · bronzeAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
What it found
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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.
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.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- A combination of low TMB and PD-L1 expression predict poor progression-free survival of metastatic melanoma patients treated with first-line ipilimumab plus nivolumab.Frontiers in immunology · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- HSPB8 counteracts tumor activity of BRAF- and NRAS-mutant melanoma cells by modulation of RAS-prenylation and autophagy.Cell death & disease · 2022Article
- Integrated molecular drivers coordinate biological and clinical states in melanoma.Nature genetics · 2020Article
- NRAS Q61R and BRAF G466A mutations in atypical melanocytic lesions newly arising in advanced melanoma patients treated with vemurafenib.Journal of cutaneous pathology · 2019Article
- Metastatic Melanoma of Uncertain Primary with 5-Year Durable Response after Conventional Therapy: A Case Report with Literature Review.Case reports in oncological medicine · 2018Article
- Tolerability of oral sorafenib in pet dogs with a diagnosis of cancer.Veterinary medicine (Auckland, N.Z.) · 2017Article
- Identification of a Novel Pathogenic Germline KDR Variant in Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Inhibition of Cell Proliferation in an NRAS Mutant Melanoma Cell Line by Combining Sorafenib and α-Mangostin.PloS one · 2016Article
- Real-time tests of multiple genome alterations take the first steps into the clinic: a learning example.OncoTargets and therapy · 2016Article
- Germline determinants of clinical outcome of cutaneous melanoma.Pigment cell & melanoma research · 2016Review
- Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model.Journal of experimental & clinical cancer research : CR · 2015Article
- Article
- Beyond BRAF: where next for melanoma therapy?British journal of cancer · 2015Review
- Article
- MicroRNA expression profiling predicts clinical outcome of carboplatin/paclitaxel-based therapy in metastatic melanoma treated on the ECOG-ACRIN trial E2603.Clinical epigenetics · 2015Article
- Amuvatinib has cytotoxic effects against NRAS-mutant melanoma but not BRAF-mutant melanoma.Melanoma research · 2014Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 1 country.
Melissa A WilsonAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut.
Fengmin ZhaoAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut.
Richard LetreroAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut.
Kurt D'AndreaAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut.
David L RimmAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut.
John M KirkwoodAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut.
Harriet M KlugerAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut.
Sandra J LeeAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut.
Lynn M SchuchterAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, ConnecticutAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut.
Keith T FlahertyAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut.
Katherine L NathansonAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, ConnecticutAuthors' Affiliations: Hematology/Oncology, Department of Medicine, University of Pennsylvania; Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania; Abramson Cancer Center of the University of Pennsylvania, Philadelphia; University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Dana Farber Cancer Institute; Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Yale University School of Medicine; and Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut knathans@exchange.upenn.edu.
Yale University · USDana-Farber Cancer Institute · USYale Cancer Center · USMassachusetts General Hospital · USUPMC Hillman Cancer Center · US
Funding
Project-006U10CA180820 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI Peter J ODwyer, MITCHELL D. SCHNALL · 2014 to 2026
$167.6MECOG OPERATIONS OFFICE (IBCSG)U10CA021115 · NCI · UNIVERSITY OF WISCONSIN MADISON · PI COMIS, ROBERT L · 1985 to 2013
$132.6MStatistics CoreU10CA180794 · NCI · DANA-FARBER CANCER INST · PI PAUL J CATALANO, CONSTANTINE A. GATSONIS · 2014 to 2026
$111.2MECOG Statistical Office Data Management GrantU10CA066636 · NCI · FRONTIER SCI &TECHNOLOGY RSCH FDN, INC · PI GRAY, ROBERT J · 1994 to 2013
$39.5MPROVIDE STATISTICAL SERVICESU10CA023318 · NCI · DANA-FARBER CANCER INSTITUTE · PI GRAY, ROBERT J · 1985 to 2013
$33.4MTherapuetic Immune Targeting of EphA2 Expressed by Melanoma & Its Tumor-AssociateP50CA121973 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KIRKWOOD, JOHN MUNN · 2008 to 2018
$22.9MCANCER RESEARCH TRAINING PROGRAMT32CA009615 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Gregory L Beatty, MICHAEL D HOGARTY · 1988 to 2026
$10.4MECOG Specimen BankingU24CA114737 · NCI · FRONTIER SCI &TECHNOLOGY RSCH FDN, INC · PI COMIS, ROBERT L · 2005 to 2014
$9.3MNCI NCTN-Network Lead Academic Participating Site at UPMC Hillman Cancer CenterUG1CA233184 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ADAM M BRUFSKY, John Munn Kirkwood · 2019 to 2026
$7.7MONCOLOGYU10CA015488 · NCI · UNIVERSITY OF PENNSYLVANIA · PI LUGER, SELINA M · 1985 to 2013
$5.6MNCI NCTN-Network Lead Academic Site at UPCIU10CA180844 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BRUFSKY, ADAM M, EDWARDS, ROBERT PAGE · 2014 to 2018
$4.5MONCOLOGYU10CA039229 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KIRKWOOD, JOHN MUNN · 1985 to 2013
$3.3MNCI NIH HHS CA14958NCI NIH HHS CA15488NCI NIH HHS CA21115NCI NIH HHS CA23318NCI NIH HHS CA39229NCI NIH HHS CA66636NCI NIH HHS P50 CA121973NCI NIH HHS R01 CA115756NCI NIH HHS R01 CA118871NCI NIH HHS R01CA118871NCI NIH HHS T32 CA009615NCI NIH HHS U10 CA014958NCI NIH HHS U10 CA015488NCI NIH HHS U10 CA021115NCI NIH HHS U10 CA023318NCI NIH HHS U10 CA039229NCI NIH HHS U10 CA066636NCI NIH HHS U10 CA180794NCI NIH HHS U10 CA180820NCI NIH HHS U10 CA180844NCI NIH HHS U24 CA114737NCI NIH HHS UG1 CA233184
Abstract
purposeSorafenib is an inhibitor of VEGF receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and RAF kinases, amongst others. We assessed the association of somatic mutations with clinicopathologic features and clinical outcomes in patients with metastatic melanoma treated on E2603, comparing treatment with carboplatin, paclitaxel ± sorafenib (CP vs. CPS) EXPERIMENTAL
designPretreatment tumor samples from 179 unique individuals enrolled on E2603 were analyzed. Genotyping was performed using a custom iPlex panel interrogating 74 mutations in 13 genes. Statistical analysis was performed using Fisher exact test, logistic regression, and Cox proportional hazards models. Progression-free survival (PFS) and overall survival were estimated using Kaplan-Meier methods.
resultsBRAF and NRAS mutations were found at frequencies consistent with other metastatic melanoma cohorts. BRAF-mutant melanoma was associated with worse performance status, increased number of disease sites, and younger age at diagnosis. NRAS-mutant melanoma was associated with better performance status, fewer sites of disease, and female gender. BRAF and NRAS mutations were not significantly predictive of response or survival when treated with CPS versus CP. However, patients with NRAS-mutant melanoma trended toward a worse response and PFS on CP than those with BRAF-mutant or WT/WT melanoma, an association that was reversed for this group on the CPS arm.
conclusionsThis study of somatic mutations in melanoma is the last prospectively collected phase III clinical trial population before the era of BRAF-targeted therapy. A trend toward improved clinical response in patients with NRAS-mutant melanoma treated with CPS was observed, possibly due to the effect of sorafenib on CRAF.
Indexed as
AdultAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinDouble-Blind MethodFemaleFollow-Up StudiesGenotypeGTP PhosphohydrolasesHumansMaleMelanomaMembrane ProteinsMiddle AgedMutationNeoplasm StagingBiomarkers, TumorBRAF protein, humanCarboplatinGTP PhosphohydrolasesMembrane ProteinsNiacinamideNRAS protein, humanPaclitaxelPhenylurea CompoundsProto-Oncogene Proteins B-rafSorafenib
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