Evidence map›Paper›PMID 37597246›Full record

Trial reportThe oncologist2023

Phase Ib/II Study of the Efficacy and Safety of Binimetinib (MEK162) Plus Panitumumab for Mutant or Wild-Type RAS Metastatic Colorectal Cancer.

Eric Van Cutsem, Rona Yaeger, Jean-Pierre Delord, Josep Tabernero, Lillian L Siu, Michel Ducreux, Salvatore Siena, Elena Elez, Stefan Kasper, Thomas Zander and 4 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIClinical Trial, Phase I
In one paragraph

Trial report in The oncologist, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01927341 (A Phase Ib/II, Open-label, Multi-center, Dose Escalation Study of MEK162 in Combination With Panitumumab in Adult Patients With Mutant RAS or Wild-type RAS Metastatic Colorectal Cancer), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 23% 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.

NCT01927341 phase1 / phase2completednot on this map

A Phase Ib/II, Open-label, Multi-center, Dose Escalation Study of MEK162 in Combination With Panitumumab in Adult Patients With Mutant RAS or Wild-type RAS Metastatic Colorectal Cancer

TypeinterventionalSponsorPfizerRan2013 to 2016Enrolled53ConditionsMetastatic Colorectal CancerArmsMEK162, Panitumumab
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Review
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

14 authors at 12 institutions in 8 countries.

Eric Van CutsemDigestive Oncology, University Hospitals Gasthuisberg, Leuven and KU Leuven, Leuven, Belgium.ORCID 0000-0002-6372-1230
Rona YaegerDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-7233-5454
Jean-Pierre DelordMedical Oncology Department, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France.
Josep TaberneroMedical Oncology Department, Vall d'Hebron Campus Hospital and Institute of Oncology (VHIO), IOB-Quiron, UVic-UICC, Barcelona, Spain.ORCID 0000-0002-2495-8139
Lillian L SiuDivision of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0002-3500-0540
Michel DucreuxDepartment of Medical Oncology, Gustave Roussy, Cancer Campus, Université Paris-Saclay, Villejuif, France.
Salvatore SienaDepartment of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy.
Elena ElezMedical Oncology Department, Vall d'Hebron Campus Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.ORCID 0000-0002-4653-6324
Stefan KasperWest German Cancer Center, Department of Medical Oncology, University Hospital Essen, Essen, Germany.
Thomas ZanderDepartment of Internal Medicine, Center for Integrated Oncology Aachen-Bonn-Cologne, University of Cologne, Duesseldorf, Germany.
Neeltje SteeghsDepartment of Medical Oncology and Clinical Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Danielle MurphyTranslational Oncology, Pfizer, La Jolla, CA, USA.
Michelle EdwardsNorth American Medical Affairs, Pfizer, New York, NY, USA.
Zev A WainbergDivision of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Pfizer (United States) · USEssen University Hospital · DEInstitut Claudius Regaud · FRKU Leuven · BEMemorial Sloan Kettering Cancer Center · USThe Netherlands Cancer Institute · NLUniversitat Autònoma de Barcelona · ESUniversité Paris-Saclay · FRUniversity Health Network · CAUniversity of California, Los Angeles · USUniversity of Cologne · DEUniversity of Milan · IT

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

introductionActivating RAS gene mutations occur in approximately 55% of patients with metastatic colorectal cancer (mCRC) and are associated with poorer clinical outcomes due to epidermal growth factor receptor (EGFR) blockade resistance. Combined EGFR and mitogen-activated protein kinase (MEK) inhibition may extend response to EGFR inhibition and overcome acquired resistance. This phase Ib/II dose escalation trial evaluated the safety and activity of dual inhibition with binimetinib (MEK1/2 inhibitor) and panitumumab (EGFR inhibitor [EGFRi]) in patients with RAS mutant or BRAF wild type (WT)/RAS WT mCRC.

methodsPhase Ib dose escalation started with binimetinib 45 mg twice daily plus panitumumab 6 mg/kg administered every 2 weeks. In the phase II study, patients with measurable mCRC were enrolled into 4 groups based on previous anti-EGFR monoclonal antibody therapy and RAS mutational status.

resultsNo patients in the phase Ib portion (n = 10) had a response; 70% of patients had stable disease. In the phase II portion (n = 43), overall response rate (ORR, confirmed) was 2.3% with one partial response in the RAS WT group, DCR was 30.2%, and median progression-free survival was 1.8 months (95%CI, 1.6-3.3). All patients experienced ≥1 adverse event, with the most common being diarrhea (71.7%), vomiting (52.8%), nausea (50.9%), fatigue (49.1%), dermatitis acneiform (43.4%), and rash (41.5%). Most patients required treatment interruption or dose reduction due to difficulties tolerating treatment.

conclusionsThe combination of binimetinib and panitumumab had substantial toxicity and limited clinical activity for patients with mutant or WT RAS mCRC, independent of EGFRi treatment history (Trial registration: NCT01927341).

Indexed as

Colonic NeoplasmsColorectal NeoplasmsRectal NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesErbB ReceptorsHumansPanitumumabProto-Oncogene Proteins p21(ras)BenzimidazolesbinimetinibErbB ReceptorsPanitumumabProto-Oncogene Proteins p21(ras)binimetinibcolorectal cancerpanitumumabRAS mutationRAS wild type

Identifiers

PMID37597246
PMCPMC10712701
OpenAlexW4386002127

What OpenQuestion holds

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LicenceCC BY
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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.