Evidence map›Paper›PMID 37059834›Full record

Trial reportNature medicine2023

Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial.

Vivek Subbiah, Robert J Kreitman, Zev A Wainberg, Anas Gazzah, Ulrik Lassen, Alexander Stein, Patrick Y Wen, Sascha Dietrich, Maja J A de Jonge, Jean-Yves Blay and 13 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02034110 (A Phase II, Open-label, Study in Subjects With BRAF V600E-Mutated Rare Cancers With Several Histologies to Investigate the Clinical Efficacy and Safety of the Combination Therapy of Dabrafenib and Trametinib), which is not on this map. Cited by 209 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
209citing papers in PubMed, 9 pooled it
41.2field-weighted citation impact, top 1% 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.

NCT02034110 phase2completednot on this map

A Phase II, Open-label, Study in Subjects With BRAF V600E-Mutated Rare Cancers With Several Histologies to Investigate the Clinical Efficacy and Safety of the Combination Therapy of Dabrafenib and Trametinib

TypeinterventionalSponsorNovartis PharmaceuticalsRan2014 to 2021Enrolled206ConditionsCancerArmsDabrafenib, Trametinib
3 · Its place in the literature

Who cites it

209 citing papers in PubMed, 9 syntheses or guidelines pooled it, 268 citations in OpenAlex.

  1. Pooled it
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  4. Efficacy and safety of dabrafenib plus trametinib in pediatric versus adult gliomas: a systematic review and meta-analysis.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025
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  19. Bridging pediatric and adult neuro-oncology: Insights into adolescents and young adults (AYA) central nervous system tumors.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
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149 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 20 institutions in 9 countries.

Vivek SubbiahDepartment of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. vsubbiah@mdanderson.org.ORCID http://orcid.org/0000-0002-6064-6837
Robert J KreitmanLaboratory of Molecular Biology, National Institutes of Health, Bethesda, MD, USA.
Zev A WainbergDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Anas GazzahDrug Development Department (DITEP), Gustave Roussy Cancer Institute, Villejuif, France.
Ulrik LassenDepartment of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-3865-4574
Alexander SteinDepartment of Internal Medicine II (Oncology Center), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Patrick Y WenCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Sascha DietrichUniversity of Heidelberg, Heidelberg, Germany.
Maja J A de JongeDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Jean-Yves BlayCenter Leon Berard & University Claude Bernard Lyon I, Lyon, France.ORCID http://orcid.org/0000-0001-7190-120X
Antoine ItalianoEarly Phase Trials and Sarcoma Units, Institut Bergonié, Bordeaux, France; Faculty of Medicine, University of Bordeaux, Bordeaux, France.ORCID http://orcid.org/0000-0002-8540-5351
Kan YonemoriNational Cancer Center Hospital, Tokyo, Japan.
Daniel C ChoNew York Medical College, Valhalla, NY, USA.
Filip Y F L de VosDepartment of Medical Oncology, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-9082-5991
Philippe MoreauDepartment of Hematology, CHU de Nantes, Nantes, France.
Elena Elez FernandezDepartment of Medical Oncology, Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), IOB-Quiron, UVic-UCC, Barcelona, Spain.ORCID http://orcid.org/0000-0002-4653-6324
Jan H M SchellensNetherlands Cancer Institute, Amsterdam, The Netherlands.
Christoph C ZielinskiMedical University of Vienna, Vienna, Austria.
Suman RedhuGlobal Program Biostatistics, Novartis Oncology, Cambridge, MA, USA.
Aislyn BoranGlobal Drug Development, Oncology Development Unit, Novartis Services, Inc., East Hanover, NJ, USA.
Vanessa Q PassosGlobal Drug Development, Oncology Development Unit, Novartis Services, Inc., East Hanover, NJ, USA.
Palanichamy IlankumaranGlobal Drug Development, Oncology Development Unit, Novartis Services, Inc., East Hanover, NJ, USA.
Yung-Jue BangSeoul National University College of Medicine, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0001-6000-4597
Center for Global Development · USCenter for Neuro-Oncology · USCentre Hospitalier Universitaire de Nantes · FRErasmus MC Cancer Institute · NLHeidelberg University · DEInstitut Gustave Roussy · FRMedical University of Vienna · ATNational Institutes of Health · USNew York Medical College · USNovartis (United States) · USSeoul National University · KRThe Netherlands Cancer Institute · NLThe University of Texas MD Anderson Cancer Center · USTokyo National Hospital · JPUniversitat de Vic - Universitat Central de Catalunya · ESUniversität Hamburg · DEUniversité Claude Bernard Lyon 1 · FRUniversité de Bordeaux · FRUniversity of California, Los Angeles · USUniversity of Copenhagen · DK

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Development of Recombinant Toxins to Treat Hematologic MalignanciesZIABC010301 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KREITMAN, ROBERT · 2009 to 2025
$21.7M
Center for Clinical and Translational Sciences (CCTS)UL1TR000371 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$13.4M
Discovery of the next-generation RET-targeted drugs based on nicotinamide scaffoldR01CA273168 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI FUNDA MERIC-BERNSTAM, Herman O Sintim · 2022 to 2026
$2.9M
Blocking tumor progression in therapy-responsive RET aberration-associated cancerR01CA242845 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI AHNERT, JORDI RODON, MOOERS, BLAINE H. M. · 2020 to 2024
$1.9M
Informatics to enable routine personalized cancer therapyU01CA180964 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BERNSTAM, ELMER V., MERIC-BERNSTAM, FUNDA · 2013 to 2015
$964k
NCATS NIH HHS UL1 TR000371NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA242845NCI NIH HHS R01 CA273168NCI NIH HHS U01 CA180964
6 · The paper itself

Abstract

BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers: anaplastic thyroid carcinoma (n = 36), biliary tract cancer (n = 43), gastrointestinal stromal tumor (n = 1), adenocarcinoma of the small intestine (n = 3), low-grade glioma (n = 13), high-grade glioma (n = 45), hairy cell leukemia (n = 55) and multiple myeloma (n = 19). The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively. Secondary endpoints were median duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Median DoR was 14.4 months, 8.9 months, not reached, 7.7 months, not reached, 31.2 months, not reached and 11.1 months, respectively. Median PFS was 6.7 months, 9.0 months, not reached, not evaluable, 9.5 months, 5.5 months, not evaluable and 6.3 months, respectively. Median OS was 14.5 months, 13.5 months, not reached, 21.8 months, not evaluable, 17.6 months, not evaluable and 33.9 months, respectively. The most frequent (≥20% of patients) treatment-related adverse events were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%) and rash (20.4%). The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E-mutated advanced rare cancers. ClinicalTrials.gov registration: NCT02034110 .

Indexed as

AdenocarcinomaGliomaAntineoplastic Combined Chemotherapy ProtocolsHumansImidazolesMutationOximesProto-Oncogene Proteins B-rafPyridonesPyrimidinonesdabrafenibImidazolesOximesProto-Oncogene Proteins B-rafPyridonesPyrimidinonestrametinib

Identifiers

PMID37059834
PMCPMC10202803
OpenAlexW4365510427

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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.