Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2015
Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer.
Open access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
In one paragraph
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 286 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
286citing papers in PubMed, 3 pooled it
25.5field-weighted citation impact, top 1% of its field
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.
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.
Who cites it
286 citing papers in PubMed, 3 syntheses or guidelines pooled it, 507 citations in OpenAlex.
- Targeted therapy in advancedBMJ (Clinical research ed.) · 2025Pooled it
- A comprehensive overview of the molecular features and therapeutic targets in BRAFClinical and translational medicine · 2024Pooled it
- Pooled it
- Phase II Study of Dabrafenib and Trametinib in Patients With Tumors WithJCO precision oncology · 2026Trial
- Encorafenib, Cetuximab, and mFOLFOX6 inThe New England journal of medicine · 2025Trial
- Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.Nature medicine · 2025Trial
- Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial.Nature medicine · 2023Trial
- Combined PD-1, BRAF and MEK inhibition in BRAFNature medicine · 2023Trial
- Randomized Trial of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF-Mutant Metastatic Colorectal Cancer (SWOG S1406).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Trametinib Activity in Patients with Solid Tumors and Lymphomas Harboring BRAF Non-V600 Mutations or Fusions: Results from NCI-MATCH (EAY131).Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients WithJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Trial
- BRAF Inhibition inJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- New Treatment Strategy and Future Research Direction for BRAF-Mutated Cancer.Cancer science · 2026Review
- Understanding the Promise and Challenges of Tumor-Agnostic Therapy: Could One Size Really Fit All?Cancers · 2026Review
- Macrophage-Derived PDGF-BB and GDF-15 Promote Drug Resistance in KRAS-Mutant Colorectal Cancer.bioRxiv : the preprint server for biology · 2026Article
- Molecular Targeting of EGFR, BRAF, and HER2 Signaling in Colorectal Cancer: Contemporary Advances with Panitumumab, Encorafenib, and Tucatinib.Journal of clinical medicine · 2026Review
- OSBPL3 drives colorectal cancer progression via Hippo-YAP signaling and modulates MEK inhibitor sensitivity.Communications biology · 2026Article
- Cost-effectiveness analysis of triplet therapy of encorafenib, binimetinib, and cetuximab for treatment of metastatic BRAF V600E-mutated colorectal cancer in China.Frontiers in pharmacology · 2026Article
- BRAF V600E-mutated metastatic Wilms tumor with complete response to targeted RAF/MEK inhibition: a post-treatment follow-up case report.Frontiers in oncology · 2026Article
226 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
20 authors at 2 institutions in 2 countries.
Ryan B CorcoranRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE. rbcorcoran@partners.org.
Chloe E AtreyaRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Gerald S FalchookRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Eunice L KwakRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
David P RyanRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Johanna C BendellRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Omid HamidRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Wells A MessersmithRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Adil DaudRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Razelle KurzrockRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Mariaelena PierobonRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Peng SunRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Elizabeth CunninghamRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Shonda LittleRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Keith OrfordRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Monica MotwaniRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Yuchen BaiRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Kiran PatelRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Alan P VenookRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
Scott KopetzRyan B. Corcoran, Eunice L. Kwak, and David P. Ryan, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA; Chloe E. Atreya, Adil Daud, and Alan P. Venook, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco; Omid Hamid, Angeles Clinic and Research Institute, Los Angeles, CA; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver; Wells A. Messersmith, University of Colorado Cancer Center and University of Colorado, Aurora, CO; Johanna C. Bendell, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Razelle Kurzrock and Scott Kopetz, University of Texas, MD Anderson Cancer Center, Houston, TX; Mariaelena Pierobon, Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA; Peng Sun, Elizabeth Cunningham, Shonda Little, Keith Orford, Monica Motwani, and Yuchen Bai, GlaxoSmithKline, Philadelphia, PA; and Kiran Patel, Incyte, Wilmington, DE.
GlaxoSmithKline (Netherlands) · NLIncyte (United States) · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MTissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI BASS, ADAM JOEL · 2007 to 2023
$33.2MUCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Y. Chen · 1986 to 2026
$30.7MU OF TEXAS HLTH SCI CTR HOUSTON CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCESUL1RR024148 · NCRR · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2006 to 2010
$27.9MCenter for Clinical and Translational Sciences (CCTS)UL1TR000371 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$13.4MTumor Heterogeneity and Acquired Resistance to EGFR InhibitionR01CA184843 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HAMILTON, STANLEY R., KOPETZ, SCOTT · 2015 to 2019
$3.2MStress Signaling Pathways and Resistance in Colorectal CancerR01CA172670 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KOPETZ, SCOTT · 2013 to 2017
$1.6MCombination Therapy to Improve MAPK Pathway Inhibitor Efficacy in BRAF and KRAS MK08CA166510 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CORCORAN, RYAN BRUCE · 2013 to 2017
$896kTargeting of Aberrant Signaling in Patient-Derived Colorectal Cancer ModelsK08CA175153 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ATREYA, CHLOE E. · 2013 to 2017
$867kNCATS NIH HHS UL1 TR000371NCI NIH HHS CA016672NCI NIH HHS K08 CA166510NCI NIH HHS K08CA166510NCI NIH HHS K08CA175143NCI NIH HHS K08 CA175153NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA127003NCI NIH HHS P50CA127003NCI NIH HHS R01 CA172670NCI NIH HHS R01CA172670NCI NIH HHS R01 CA184843NCI NIH HHS R01CA184843NCRR NIH HHS UL1 RR024148NIDDK NIH HHS P30 DK026743
Abstract
purposeTo evaluate dabrafenib, a selective BRAF inhibitor, combined with trametinib, a selective MEK inhibitor, in patients with BRAF V600-mutant metastatic colorectal cancer (mCRC). PATIENTS AND
methodsA total of 43 patients with BRAF V600-mutant mCRC were treated with dabrafenib (150 mg twice daily) plus trametinib (2 mg daily), 17 of whom were enrolled onto a pharmacodynamic cohort undergoing mandatory biopsies before and during treatment. Archival tissues were analyzed for microsatellite instability, PTEN status, and 487-gene sequencing. Patient-derived xenografts were established from core biopsy samples.
resultsOf 43 patients, five (12%) achieved a partial response or better, including one (2%) complete response, with duration of response > 36 months; 24 patients (56%) achieved stable disease as best confirmed response. Ten patients (23%) remained in the study > 6 months. All nine evaluable during-treatment biopsies had reduced levels of phosphorylated ERK relative to pretreatment biopsies (average decrease ± standard deviation, 47% ± 24%). Mutational analysis revealed that the patient achieving a complete response and two of three evaluable patients achieving a partial response had PIK3CA mutations. Neither PTEN loss nor microsatellite instability correlated with efficacy. Responses to dabrafenib plus trametinib were comparable in patient-derived xenograft-bearing mice and the biopsied lesions from each corresponding patient.
conclusionThe combination of dabrafenib plus trametinib has activity in a subset of patients with BRAF V600-mutant mCRC. Mitogen-activated protein kinase signaling was inhibited in all patients evaluated, but to a lesser degree than observed in BRAF-mutant melanoma with dabrafenib alone. PIK3CA mutations were identified in responding patients and thus do not preclude response to this regimen. Additional studies targeting the mitogen-activated protein kinase pathway in this disease are warranted.
Indexed as
AnimalsAntineoplastic Combined Chemotherapy ProtocolsBiopsyCohort StudiesColorectal NeoplasmsFemaleFollow-Up StudiesHumansImidazolesMaleMAP Kinase Kinase 1MiceMicrosatellite InstabilityMiddle AgedMutationNeoplasm StagingBRAF protein, humandabrafenibImidazolesMAP2K1 protein, humanMAP Kinase Kinase 1OximesProto-Oncogene Proteins B-rafPTEN PhosphohydrolasePTEN protein, humanPyridonesPyrimidinonestrametinib
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