Combined vemurafenib and cobimetinib in BRAF-mutated melanoma.
Identifieur interne : 001E53 ( Ncbi/Merge ); précédent : 001E52; suivant : 001E54Combined vemurafenib and cobimetinib in BRAF-mutated melanoma.
Auteurs : James Larkin ; Paolo A. Ascierto ; Brigitte Dréno ; Victoria Atkinson ; Gabriella Liszkay ; Michele Maio ; Mario Mandalà ; Lev Demidov ; Daniil Stroyakovskiy ; Luc Thomas ; Luis De La Cruz-Merino ; Caroline Dutriaux ; Claus Garbe ; Mika A. Sovak ; Ilsung Chang ; Nicholas Choong ; Stephen P. Hack ; Grant A. Mcarthur ; Antoni RibasSource :
- The New England journal of medicine [ 1533-4406 ] ; 2014.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Azétidines (administration et posologie), Azétidines (effets indésirables), Estimation de Kaplan-Meier, Femelle, Humains, Indoles (administration et posologie), Indoles (effets indésirables), MAP Kinase Kinase 1 (antagonistes et inhibiteurs), Mutation, Mâle, Mélanome (génétique), Mélanome (mortalité), Mélanome (secondaire), Mélanome (traitement médicamenteux), Pipéridines (administration et posologie), Pipéridines (effets indésirables), Protocoles de polychimiothérapie antinéoplasique (effets indésirables), Protocoles de polychimiothérapie antinéoplasique (usage thérapeutique), Protéines proto-oncogènes B-raf (antagonistes et inhibiteurs), Protéines proto-oncogènes B-raf (génétique), Sujet âgé, Sulfonamides (administration et posologie), Sulfonamides (effets indésirables), Survie sans rechute, Taux de survie.
- MESH :
- administration et posologie : Azétidines, Indoles, Pipéridines, Sulfonamides.
- antagonistes et inhibiteurs : MAP Kinase Kinase 1, Protéines proto-oncogènes B-raf.
- effets indésirables : Azétidines, Indoles, Pipéridines, Protocoles de polychimiothérapie antinéoplasique, Sulfonamides.
- génétique : Mélanome, Protéines proto-oncogènes B-raf.
- mortalité : Mélanome.
- secondaire : Mélanome.
- traitement médicamenteux : Mélanome.
- usage thérapeutique : Protocoles de polychimiothérapie antinéoplasique.
- Adulte, Adulte d'âge moyen, Estimation de Kaplan-Meier, Femelle, Humains, Mutation, Mâle, Sujet âgé, Survie sans rechute, Taux de survie.
English descriptors
- KwdEn :
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols (adverse effects), Antineoplastic Combined Chemotherapy Protocols (therapeutic use), Azetidines (administration & dosage), Azetidines (adverse effects), Disease-Free Survival, Female, Humans, Indoles (administration & dosage), Indoles (adverse effects), Kaplan-Meier Estimate, MAP Kinase Kinase 1 (antagonists & inhibitors), Male, Melanoma (drug therapy), Melanoma (genetics), Melanoma (mortality), Melanoma (secondary), Middle Aged, Mutation, Piperidines (administration & dosage), Piperidines (adverse effects), Proto-Oncogene Proteins B-raf (antagonists & inhibitors), Proto-Oncogene Proteins B-raf (genetics), Sulfonamides (administration & dosage), Sulfonamides (adverse effects), Survival Rate.
- MESH :
- chemical , administration & dosage : Azetidines, Indoles, Piperidines, Sulfonamides.
- adverse effects : Antineoplastic Combined Chemotherapy Protocols, Azetidines, Indoles, Piperidines, Sulfonamides.
- chemical , antagonists & inhibitors : MAP Kinase Kinase 1, Proto-Oncogene Proteins B-raf.
- drug therapy : Melanoma.
- genetics : Melanoma, Proto-Oncogene Proteins B-raf.
- mortality : Melanoma.
- secondary : Melanoma.
- therapeutic use : Antineoplastic Combined Chemotherapy Protocols.
- Adult, Aged, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Mutation, Survival Rate.
Abstract
The combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes in patients with melanoma by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib.
DOI: 10.1056/NEJMoa1408868
PubMed: 25265494
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 003296
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pubmed:25265494Le document en format XML
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<author><name sortKey="Larkin, James" sort="Larkin, James" uniqKey="Larkin J" first="James" last="Larkin">James Larkin</name>
<affiliation><nlm:affiliation>From Royal Marsden Hospital, London (J.L.); Istituto Nazionale Tumori Fondazione G. Pascale, Naples (P.A.A.), Azienda Ospedaliera Universitaria Senese, Siena (M. Maio), and Papa Giovanni XXIII Hospital, Bergamo (M. Mandalà) - all in Italy; Hôtel Dieu Place Alexis Ricordeau, Nantes (B.D.), Centre Hospitalier Lyon Sud, Pierre-Bénite (L.T.), and Hôpital Saint André, Bordeaux (C.D.) - all in France; Princess Alexandra Hospital, Woolloongabba, QLD (V.A.), and Peter MacCallum Cancer Centre, Melbourne, VIC (G.A.M.) - both in Australia; National Institute of Oncology, Budapest, Hungary (G.L.); N.N. Blokhin Russian Cancer Research Center, Moscow (L.D.), and Moscow City Oncology Hospital 62, Krasnogorsk (D.S.) - both in Russia; Hospital Universitario Virgen Macarena, Seville, Spain (L.C.-M.); University of Tübingen, Tübingen, Germany (C.G.); Genentech, South San Francisco, CA (M.A.S., I.C., N.C., S.P.H.); and Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles (A.R.).</nlm:affiliation>
<wicri:noCountry code="subField">Los Angeles (A.R.).</wicri:noCountry>
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<author><name sortKey="Ascierto, Paolo A" sort="Ascierto, Paolo A" uniqKey="Ascierto P" first="Paolo A" last="Ascierto">Paolo A. Ascierto</name>
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<author><name sortKey="Dreno, Brigitte" sort="Dreno, Brigitte" uniqKey="Dreno B" first="Brigitte" last="Dréno">Brigitte Dréno</name>
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<author><name sortKey="Atkinson, Victoria" sort="Atkinson, Victoria" uniqKey="Atkinson V" first="Victoria" last="Atkinson">Victoria Atkinson</name>
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<author><name sortKey="Liszkay, Gabriella" sort="Liszkay, Gabriella" uniqKey="Liszkay G" first="Gabriella" last="Liszkay">Gabriella Liszkay</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Combined vemurafenib and cobimetinib in BRAF-mutated melanoma.</title>
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<affiliation><nlm:affiliation>From Royal Marsden Hospital, London (J.L.); Istituto Nazionale Tumori Fondazione G. Pascale, Naples (P.A.A.), Azienda Ospedaliera Universitaria Senese, Siena (M. Maio), and Papa Giovanni XXIII Hospital, Bergamo (M. Mandalà) - all in Italy; Hôtel Dieu Place Alexis Ricordeau, Nantes (B.D.), Centre Hospitalier Lyon Sud, Pierre-Bénite (L.T.), and Hôpital Saint André, Bordeaux (C.D.) - all in France; Princess Alexandra Hospital, Woolloongabba, QLD (V.A.), and Peter MacCallum Cancer Centre, Melbourne, VIC (G.A.M.) - both in Australia; National Institute of Oncology, Budapest, Hungary (G.L.); N.N. Blokhin Russian Cancer Research Center, Moscow (L.D.), and Moscow City Oncology Hospital 62, Krasnogorsk (D.S.) - both in Russia; Hospital Universitario Virgen Macarena, Seville, Spain (L.C.-M.); University of Tübingen, Tübingen, Germany (C.G.); Genentech, South San Francisco, CA (M.A.S., I.C., N.C., S.P.H.); and Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles (A.R.).</nlm:affiliation>
<wicri:noCountry code="subField">Los Angeles (A.R.).</wicri:noCountry>
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<author><name sortKey="De La Cruz Merino, Luis" sort="De La Cruz Merino, Luis" uniqKey="De La Cruz Merino L" first="Luis" last="De La Cruz-Merino">Luis De La Cruz-Merino</name>
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<author><name sortKey="Chang, Ilsung" sort="Chang, Ilsung" uniqKey="Chang I" first="Ilsung" last="Chang">Ilsung Chang</name>
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<author><name sortKey="Choong, Nicholas" sort="Choong, Nicholas" uniqKey="Choong N" first="Nicholas" last="Choong">Nicholas Choong</name>
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<author><name sortKey="Hack, Stephen P" sort="Hack, Stephen P" uniqKey="Hack S" first="Stephen P" last="Hack">Stephen P. Hack</name>
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<author><name sortKey="Mcarthur, Grant A" sort="Mcarthur, Grant A" uniqKey="Mcarthur G" first="Grant A" last="Mcarthur">Grant A. Mcarthur</name>
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<author><name sortKey="Ribas, Antoni" sort="Ribas, Antoni" uniqKey="Ribas A" first="Antoni" last="Ribas">Antoni Ribas</name>
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<series><title level="j">The New England journal of medicine</title>
<idno type="eISSN">1533-4406</idno>
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<term>Azetidines (adverse effects)</term>
<term>Disease-Free Survival</term>
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<term>Humans</term>
<term>Indoles (administration & dosage)</term>
<term>Indoles (adverse effects)</term>
<term>Kaplan-Meier Estimate</term>
<term>MAP Kinase Kinase 1 (antagonists & inhibitors)</term>
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<term>Melanoma (genetics)</term>
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<term>Azétidines (administration et posologie)</term>
<term>Azétidines (effets indésirables)</term>
<term>Estimation de Kaplan-Meier</term>
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<term>Indoles (effets indésirables)</term>
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<term>Mâle</term>
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<term>Mélanome (traitement médicamenteux)</term>
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<term>Taux de survie</term>
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<term>Protéines proto-oncogènes B-raf</term>
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<front><div type="abstract" xml:lang="en">The combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes in patients with melanoma by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25265494</PMID>
<DateCreated><Year>2014</Year>
<Month>11</Month>
<Day>13</Day>
</DateCreated>
<DateCompleted><Year>2014</Year>
<Month>12</Month>
<Day>03</Day>
</DateCompleted>
<DateRevised><Year>2016</Year>
<Month>11</Month>
<Day>25</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1533-4406</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>371</Volume>
<Issue>20</Issue>
<PubDate><Year>2014</Year>
<Month>Nov</Month>
<Day>13</Day>
</PubDate>
</JournalIssue>
<Title>The New England journal of medicine</Title>
<ISOAbbreviation>N. Engl. J. Med.</ISOAbbreviation>
</Journal>
<ArticleTitle>Combined vemurafenib and cobimetinib in BRAF-mutated melanoma.</ArticleTitle>
<Pagination><MedlinePgn>1867-76</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1056/NEJMoa1408868</ELocationID>
<Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">The combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes in patients with melanoma by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">We randomly assigned 495 patients with previously untreated unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma to receive vemurafenib and cobimetinib (combination group) or vemurafenib and placebo (control group). The primary end point was investigator-assessed progression-free survival.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">The median progression-free survival was 9.9 months in the combination group and 6.2 months in the control group (hazard ratio for death or disease progression, 0.51; 95% confidence interval [CI], 0.39 to 0.68; P<0.001). The rate of complete or partial response in the combination group was 68%, as compared with 45% in the control group (P<0.001), including rates of complete response of 10% in the combination group and 4% in the control group. Progression-free survival as assessed by independent review was similar to investigator-assessed progression-free survival. Interim analyses of overall survival showed 9-month survival rates of 81% (95% CI, 75 to 87) in the combination group and 73% (95% CI, 65 to 80) in the control group. Vemurafenib and cobimetinib was associated with a nonsignificantly higher incidence of adverse events of grade 3 or higher, as compared with vemurafenib and placebo (65% vs. 59%), and there was no significant difference in the rate of study-drug discontinuation. The number of secondary cutaneous cancers decreased with the combination therapy.</AbstractText>
<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">The addition of cobimetinib to vemurafenib was associated with a significant improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma, at the cost of some increase in toxicity. (Funded by F. Hoffmann-La Roche/Genentech; coBRIM ClinicalTrials.gov number, NCT01689519.).</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Larkin</LastName>
<ForeName>James</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>From Royal Marsden Hospital, London (J.L.); Istituto Nazionale Tumori Fondazione G. Pascale, Naples (P.A.A.), Azienda Ospedaliera Universitaria Senese, Siena (M. Maio), and Papa Giovanni XXIII Hospital, Bergamo (M. Mandalà) - all in Italy; Hôtel Dieu Place Alexis Ricordeau, Nantes (B.D.), Centre Hospitalier Lyon Sud, Pierre-Bénite (L.T.), and Hôpital Saint André, Bordeaux (C.D.) - all in France; Princess Alexandra Hospital, Woolloongabba, QLD (V.A.), and Peter MacCallum Cancer Centre, Melbourne, VIC (G.A.M.) - both in Australia; National Institute of Oncology, Budapest, Hungary (G.L.); N.N. Blokhin Russian Cancer Research Center, Moscow (L.D.), and Moscow City Oncology Hospital 62, Krasnogorsk (D.S.) - both in Russia; Hospital Universitario Virgen Macarena, Seville, Spain (L.C.-M.); University of Tübingen, Tübingen, Germany (C.G.); Genentech, South San Francisco, CA (M.A.S., I.C., N.C., S.P.H.); and Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles (A.R.).</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ascierto</LastName>
<ForeName>Paolo A</ForeName>
<Initials>PA</Initials>
</Author>
<Author ValidYN="Y"><LastName>Dréno</LastName>
<ForeName>Brigitte</ForeName>
<Initials>B</Initials>
</Author>
<Author ValidYN="Y"><LastName>Atkinson</LastName>
<ForeName>Victoria</ForeName>
<Initials>V</Initials>
</Author>
<Author ValidYN="Y"><LastName>Liszkay</LastName>
<ForeName>Gabriella</ForeName>
<Initials>G</Initials>
</Author>
<Author ValidYN="Y"><LastName>Maio</LastName>
<ForeName>Michele</ForeName>
<Initials>M</Initials>
</Author>
<Author ValidYN="Y"><LastName>Mandalà</LastName>
<ForeName>Mario</ForeName>
<Initials>M</Initials>
</Author>
<Author ValidYN="Y"><LastName>Demidov</LastName>
<ForeName>Lev</ForeName>
<Initials>L</Initials>
</Author>
<Author ValidYN="Y"><LastName>Stroyakovskiy</LastName>
<ForeName>Daniil</ForeName>
<Initials>D</Initials>
</Author>
<Author ValidYN="Y"><LastName>Thomas</LastName>
<ForeName>Luc</ForeName>
<Initials>L</Initials>
</Author>
<Author ValidYN="Y"><LastName>de la Cruz-Merino</LastName>
<ForeName>Luis</ForeName>
<Initials>L</Initials>
</Author>
<Author ValidYN="Y"><LastName>Dutriaux</LastName>
<ForeName>Caroline</ForeName>
<Initials>C</Initials>
</Author>
<Author ValidYN="Y"><LastName>Garbe</LastName>
<ForeName>Claus</ForeName>
<Initials>C</Initials>
</Author>
<Author ValidYN="Y"><LastName>Sovak</LastName>
<ForeName>Mika A</ForeName>
<Initials>MA</Initials>
</Author>
<Author ValidYN="Y"><LastName>Chang</LastName>
<ForeName>Ilsung</ForeName>
<Initials>I</Initials>
</Author>
<Author ValidYN="Y"><LastName>Choong</LastName>
<ForeName>Nicholas</ForeName>
<Initials>N</Initials>
</Author>
<Author ValidYN="Y"><LastName>Hack</LastName>
<ForeName>Stephen P</ForeName>
<Initials>SP</Initials>
</Author>
<Author ValidYN="Y"><LastName>McArthur</LastName>
<ForeName>Grant A</ForeName>
<Initials>GA</Initials>
</Author>
<Author ValidYN="Y"><LastName>Ribas</LastName>
<ForeName>Antoni</ForeName>
<Initials>A</Initials>
</Author>
</AuthorList>
<Language>eng</Language>
<DataBankList CompleteYN="Y"><DataBank><DataBankName>ClinicalTrials.gov</DataBankName>
<AccessionNumberList><AccessionNumber>NCT01689519</AccessionNumber>
</AccessionNumberList>
</DataBank>
</DataBankList>
<PublicationTypeList><PublicationType UI="D017428">Clinical Trial, Phase III</PublicationType>
<PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D016448">Multicenter Study</PublicationType>
<PublicationType UI="D016449">Randomized Controlled Trial</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2014</Year>
<Month>09</Month>
<Day>29</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>N Engl J Med</MedlineTA>
<NlmUniqueID>0255562</NlmUniqueID>
<ISSNLinking>0028-4793</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D001384">Azetidines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C574276">GDC-0973</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007211">Indoles</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D010880">Piperidines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D013449">Sulfonamides</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>207SMY3FQT</RegistryNumber>
<NameOfSubstance UI="C551177">vemurafenib</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber>
<NameOfSubstance UI="D048493">Proto-Oncogene Proteins B-raf</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.12.2</RegistryNumber>
<NameOfSubstance UI="D048369">MAP Kinase Kinase 1</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>AIM</CitationSubset>
<CitationSubset>IM</CitationSubset>
<CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Nat Rev Clin Oncol. 2014 Dec;11(12):683</RefSource>
<PMID Version="1">25331181</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="CommentIn"><RefSource>N Engl J Med. 2014 Nov 13;371(20):1929-30</RefSource>
<PMID Version="1">25390744</PMID>
</CommentsCorrections>
</CommentsCorrectionsList>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000971" MajorTopicYN="N">Antineoplastic Combined Chemotherapy Protocols</DescriptorName>
<QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001384" MajorTopicYN="N">Azetidines</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName>
<QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018572" MajorTopicYN="N">Disease-Free Survival</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007211" MajorTopicYN="N">Indoles</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName>
<QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D053208" MajorTopicYN="N">Kaplan-Meier Estimate</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D048369" MajorTopicYN="N">MAP Kinase Kinase 1</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008545" MajorTopicYN="N">Melanoma</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName>
<QualifierName UI="Q000556" MajorTopicYN="N">secondary</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010880" MajorTopicYN="N">Piperidines</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName>
<QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D048493" MajorTopicYN="N">Proto-Oncogene Proteins B-raf</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013449" MajorTopicYN="N">Sulfonamides</DescriptorName>
<QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName>
<QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015996" MajorTopicYN="N">Survival Rate</DescriptorName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2014</Year>
<Month>9</Month>
<Day>30</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2014</Year>
<Month>9</Month>
<Day>30</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="medline"><Year>2014</Year>
<Month>12</Month>
<Day>15</Day>
<Hour>6</Hour>
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<PublicationStatus>ppublish</PublicationStatus>
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<ArticleId IdType="doi">10.1056/NEJMoa1408868</ArticleId>
</ArticleIdList>
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<affiliations><list></list>
<tree><noCountry><name sortKey="Ascierto, Paolo A" sort="Ascierto, Paolo A" uniqKey="Ascierto P" first="Paolo A" last="Ascierto">Paolo A. Ascierto</name>
<name sortKey="Atkinson, Victoria" sort="Atkinson, Victoria" uniqKey="Atkinson V" first="Victoria" last="Atkinson">Victoria Atkinson</name>
<name sortKey="Chang, Ilsung" sort="Chang, Ilsung" uniqKey="Chang I" first="Ilsung" last="Chang">Ilsung Chang</name>
<name sortKey="Choong, Nicholas" sort="Choong, Nicholas" uniqKey="Choong N" first="Nicholas" last="Choong">Nicholas Choong</name>
<name sortKey="De La Cruz Merino, Luis" sort="De La Cruz Merino, Luis" uniqKey="De La Cruz Merino L" first="Luis" last="De La Cruz-Merino">Luis De La Cruz-Merino</name>
<name sortKey="Demidov, Lev" sort="Demidov, Lev" uniqKey="Demidov L" first="Lev" last="Demidov">Lev Demidov</name>
<name sortKey="Dreno, Brigitte" sort="Dreno, Brigitte" uniqKey="Dreno B" first="Brigitte" last="Dréno">Brigitte Dréno</name>
<name sortKey="Dutriaux, Caroline" sort="Dutriaux, Caroline" uniqKey="Dutriaux C" first="Caroline" last="Dutriaux">Caroline Dutriaux</name>
<name sortKey="Garbe, Claus" sort="Garbe, Claus" uniqKey="Garbe C" first="Claus" last="Garbe">Claus Garbe</name>
<name sortKey="Hack, Stephen P" sort="Hack, Stephen P" uniqKey="Hack S" first="Stephen P" last="Hack">Stephen P. Hack</name>
<name sortKey="Larkin, James" sort="Larkin, James" uniqKey="Larkin J" first="James" last="Larkin">James Larkin</name>
<name sortKey="Liszkay, Gabriella" sort="Liszkay, Gabriella" uniqKey="Liszkay G" first="Gabriella" last="Liszkay">Gabriella Liszkay</name>
<name sortKey="Maio, Michele" sort="Maio, Michele" uniqKey="Maio M" first="Michele" last="Maio">Michele Maio</name>
<name sortKey="Mandala, Mario" sort="Mandala, Mario" uniqKey="Mandala M" first="Mario" last="Mandalà">Mario Mandalà</name>
<name sortKey="Mcarthur, Grant A" sort="Mcarthur, Grant A" uniqKey="Mcarthur G" first="Grant A" last="Mcarthur">Grant A. Mcarthur</name>
<name sortKey="Ribas, Antoni" sort="Ribas, Antoni" uniqKey="Ribas A" first="Antoni" last="Ribas">Antoni Ribas</name>
<name sortKey="Sovak, Mika A" sort="Sovak, Mika A" uniqKey="Sovak M" first="Mika A" last="Sovak">Mika A. Sovak</name>
<name sortKey="Stroyakovskiy, Daniil" sort="Stroyakovskiy, Daniil" uniqKey="Stroyakovskiy D" first="Daniil" last="Stroyakovskiy">Daniil Stroyakovskiy</name>
<name sortKey="Thomas, Luc" sort="Thomas, Luc" uniqKey="Thomas L" first="Luc" last="Thomas">Luc Thomas</name>
</noCountry>
</tree>
</affiliations>
</record>
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