Phase Ib/II Study of the Efficacy and Safety of Binimetinib (MEK162) Plus Panitumumab for Mutant or Wild-Type RAS Metastatic Colorectal Cancer
Van Cutsem, Eric (University Hospitals Gasthuisberg (Leuven, Bèlgica))
Yaeger, Rona (Memorial Sloan Kettering Cancer Center (New York, Regne Unit))
Delord, Jean-Pierre (Institut Claudius Regaud (Toulouse, France))
Tabernero, Josep (Vall d'Hebron Institut d'Oncologia)
Siu, Lillian L. (University Health Network (Toronto, Canadà))
Ducreux, Michel (Université Paris-Saclay (Villejuif, França))
Siena, Salvatore (Università degli Studi di Milano)
Elez, Elena (Universitat Autònoma de Barcelona)
Kasper, Stefan (University Hospital Essen (Alemanya))
Zander, Thomas (University of Cologne)
Steeghs, Neeltje (The Netherlands Cancer Institute (Amsterdam, Països Baixos))
Murphy, Danielle (Pfizer (La Jolla, Estats Units d'Amèrica))
Edwards, Michelle (Pfizer (New York, Estats Units d'Amèrica))
Wainberg, Zev A. (David Geffen School of Medicine at UCLA (Los Angeles, Estats Units d'Amèrica))

Data:	2023
Resum:	Activating 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. Phase 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. No 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. The 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). This article reports the results of a study that evaluated the combination of the MEK1/2 inhibitor binimetinib and the EGFR inhibitor panitumumab in patients with RAS -mutant or BRAF wild type/ RAS wild-type metastatic colorectal cancer.
Ajuts:	National Institutes of Health Cancer Center P30 CA 008748
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Binimetinib ; Panitumumab ; Colorectal cancer ; RAS mutation ; RAS wild type
Publicat a:	The Oncologist, Vol. 28 (august 2023) , p. e1209-e1218, ISSN 1549-490X

DOI: 10.1093/oncolo/oyad210
PMID: 37597246

10 p, 2.0 MB

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