Phase Ib/II Study of the Efficacy and Safety of Binimetinib (MEK162) Plus Panitumumab for Mutant or Wild-Type RAS Metastatic Colorectal Cancer
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Introduction: 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. Methods: 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. Results: 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. Conclusions: 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).
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A phase Ib/II study combining MEK inhibitors with anti-EGFR agents yielded an objective response rate of 6.7% while severe toxicities were observed in 30-62.5% of cases.
“Consequently, a phase Ib/II study combining MEK inhibitors with anti-EGFR agents was planned, but it yielded an objective response rate of 6.7% while severe toxicities were observed in 30–62.5% of cases [81].”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [81]
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Cites
Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer
Misale, S., Yaeger, R., Hobor, S., Scala, E., Janakiraman, M., Liska, D., Valtorta, E., Schiavo, R., Buscarino, M., Siravegna, G., et al. (2012) · Nature · doi:10.1038/nature11156 · Cited by 1,889 · see citing works
Self-citationThe molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers
Diaz Jr, L. A., Williams, R. T., Wu, J., Kinde, I., Hecht, J. R., Berlin, J., Allen, B., Bozic, I., Reiter, J. G., Nowak, M. A., et al. (2012) · Nature · doi:10.1038/nature11219 · Cited by 1,713 · see citing works
Encorafenib, Binimetinib, and Cetuximab in <i>BRAF</i> V600E–Mutated Colorectal Cancer
Kopetz, S., Grothey, A., Yaeger, R., Van Cutsem, E., Desai, J., Yoshino, T., Wasan, H., Ciardiello, F., Loupakis, F., Hong, Y. S., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1908075 · Cited by 1,491 · see citing works
Self-citationVan Cutsem, E., Cervantes, A., Nordlinger, B., & Arnold, D. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu260 · Cited by 1,167 · see citing works
Self-citationClonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients
Siravegna, G., Mussolin, B., Buscarino, M., Corti, G., Cassingena, A., Crisafulli, G., Ponzetti, A., Cremolini, C., Amatu, A., Lauricella, C., et al. (2015) · Nature Medicine · doi:10.1038/nm.3870 · Cited by 1,079 · see citing works
Self-citationArnold, D., Lueza, B., Douillard, J.-Y., Peeters, M., Lenz, H., Venook, A. P., Heinemann, V., Cutsem, E. V., Pignon, J., Tabernero, J. M., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx175 · Cited by 837 · see citing works
Self-citationCombined BRAF, EGFR, and MEK Inhibition in Patients with <i>BRAF</i> V600E-Mutant Colorectal Cancer
Corcoran, R. B., André, T., Atreya, C. E., Schellens, J. H. M., Yoshino, T., Bendell, J. C., Hollebecque, A., McRee, A. J., Siena, S., Middleton, G., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1226 · Cited by 592 · see citing works
Self-citationTabernero, J., Grothey, A., Van Cutsem, E., Yaeger, R., Wasan, H., Yoshino, T., Desai, J., Ciardiello, F., Loupakis, F., Hong, Y. S., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.20.02088 · Cited by 569 · see citing works
Self-citationInfante, J. R., Fecher, L. A., Falchook, G. S., Nallapareddy, S., Gordon, M. S., Becerra, C., DeMarini, D. J., Cox, D. S., Xu, Y., Morris, S. R., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70270-x · Cited by 552 · see citing works
Mechanisms of resistance to anti-EGFR therapy in colorectal cancer
Zhao, B., Wang, L., Qiu, H., Zhang, M., Sun, L., Peng, P., Yu, Q., & Yuan, X. (2017) · Oncotarget · doi:10.18632/oncotarget.14012 · Cited by 319 · see citing works
Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer
Strickler, J. H., Loree, J. M., Ahronian, L. G., Parikh, A. R., Niedzwiecki, D., Pereira, A. A. L., McKinney, M. S., Korn, W. M., Atreya, C. E., Banks, K. C., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1009 · Cited by 296 · see citing works
Arena, S., Bellosillo, B., Siravegna, G., Martínez, A., Cañadas, I., Lazzari, L., Ferruz, N., Russo, M., Misale, S., González, I., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2821 · Cited by 271 · see citing works
Misale, S., Arena, S., Lamba, S., Siravegna, G., Lallo, A., Hobor, S., Russo, M., Buscarino, M., Lazzari, L., Sartore-Bianchi, A., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007947 · Cited by 263 · see citing works
Self-citationErratum: Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients
Siravegna, G., Mussolin, B., Buscarino, M., Corti, G., Cassingena, A., Crisafulli, G., Ponzetti, A., Cremolini, C., Amatu, A., Lauricella, C., et al. (2015) · Nature Medicine · doi:10.1038/nm0715-827b · Cited by 255 · see citing works
Self-citationVan Cutsem, E., Huijberts, S., Grothey, A., Yaeger, R., Cuyle, P.-J., Elez, E., Fakih, M., Montagut, C., Peeters, M., Yoshino, T., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.18.02459 · Cited by 224 · see citing works
Self-citationBendell, J. C., Javle, M. M., Bekaii‐Saab, T., Finn, R. S., Wainberg, Z. A., Laheru, D. A., Weekes, C. D., Tan, B. R., Khan, G. N., Zalupski, M. M., et al. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.10 · Cited by 128 · see citing works
Self-citationVertical suppression of the EGFR pathway prevents onset of resistance in colorectal cancers
Misale, S., Bozic, I., Tong, J., Peraza-Penton, A., Lallo, A., Baldi, F., Lin, K. H., Truini, M., Trusolino, L., Bertotti, A., et al. (2015) · Nature Communications · doi:10.1038/ncomms9305 · Cited by 122 · see citing works
Epidermal growth factor receptor (EGFR) inhibitors for metastatic colorectal cancer
Chan, D. L. H., Segelov, E., Wong, R. S., Smith, A., Herbertson, R. A., Li, B. T., Tebbutt, N. C., Price, T. J., & Pavlakis, N. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007047.pub2 · Cited by 116 · see citing works
Mauri, G., Pizzutilo, E. G., Amatu, A., Bencardino, K. B., Palmeri, L., Bonazzina, E. F., Tosi, F., Stella, G. C., Burrafato, G., Scaglione, F., et al. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.12.006 · Cited by 89 · see citing works
Self-citationCiombor, K. K., & Bekaii‐Saab, T. (2017) · The Oncologist · doi:10.1634/theoncologist.2017-0203 · Cited by 74 · see citing works
Precision therapy in RAS mutant colorectal cancer
Dienstmann, R., Connor, K., Byrne, A. T., Fridman, W. H., Lambrechts, D., Sadanandam, A., Trusolino, L., Prehn, J. H. M., Tabernero, J., & Kolch, W. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.12.051 · Cited by 73 · see citing works
Self-citationImmune Resistance and EGFR Antagonists in Colorectal Cancer
Giordano, G., Remo, A., Porrás, A., & Pancione, M. (2019) · Cancers · doi:10.3390/cancers11081089 · Cited by 55 · see citing works
A review of binimetinib for the treatment of mutant cutaneous melanoma.
Koelblinger, P., Dornbierer, J., & Dummer, R. (2017) · Future Oncology · doi:10.2217/fon-2017-0170 · Cited by 40 · see citing works
Abstract 2515: Preclinical Development of ARRY-162, A Potent and Selective MEK 1/2 Inhibitor
Lee, P. A., Wallace, E. M., Marlow, A., Yeh, T. C., Marsh, V., Anderson, D. A., Woessner, R. D., Hurley, B., Lyssikatos, J. P., Poch, G., et al. (2010) · Cancer Research · doi:10.1158/1538-7445.am10-2515 · Cited by 36 · see citing works
Adams, R., Fisher, D. J., Farragher, S., Jasani, B., Smith, C. G., James, M. D., Cheadle, J. P., Nichols, L., Meade, A. M., Kaplan, R. S., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.30.30_suppl.32 · Cited by 27 · see citing works
Tabernero, J. M., Velez, L., Trevino, T. L., et al. (2021) · ESMO Open · doi:10.1016/j.esmoop.2021.100328 · Cited by 26 · see citing works
Self-citationPhase II Trial of Trametinib and Panitumumab in RAS/RAF Wild Type Metastatic Colorectal Cancer
Alshammari, K. M., Aung, K. L., Zhang, T., Razak, A. R. A., Serra, S., Stockley, T. L., Wang, L. E., Nguyen, J., Spreafico, A., Hansen, A. R., et al. (2021) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2021.07.004 · Cited by 15 · see citing works
Self-citationGarrido‐Laguna, I., Patel, S. B., & Gill, D. M. (2015) · OncoTargets and Therapy · doi:10.2147/ott.s68558 · Cited by 9 · see citing works
Woessner, R. D., Winski, S. L., Rana, S., et al. (2010) · Cancer Research · doi:10.1158/1538-7445.am10-2514 · Cited by 4 · see citing works
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Sütcüoğlu, O., Yıldırım, H. Ç., Almuradova, E., Günenç, D., & Yalçın, Ş. (2025) · Medicina · doi:10.3390/medicina61071202 · Cited by 10 · see citing works
- Authors
- Van Cutsem, E., Yaeger, R., Delord, J.-P., Tabernero, J., Siu, L. L., Ducreux, M., Siena, S., Elez, E., Kasper, S., Zander, T., Steeghs, N., Murphy, D., Edwards, M., & Wainberg, Z. A.
- Affiliations
- Digestive Oncology, University Hospitals Gasthuisberg , Leuven and KU Leuven, Leuven , Belgium
- Memorial Sloan Kettering Cancer Center (US)
- Institut universitaire du cancer de Toulouse Oncopole (FR)
- Vall d'Hebron Institute of Oncology (ES)
- University Health Network (CA)
- Université Paris-Saclay (FR)
- University of Milan (IT)
- Medical Oncology Department, Vall d’Hebron Campus Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona (UAB) , Barcelona , Spain
- Essen University Hospital (DE)
- University of Cologne (DE)
- The Netherlands Cancer Institute (NL)
- Pfizer (United States) (US)
- University of California, Los Angeles (US)
- ORCID
- Venue
- The Oncologist
- Publisher
- Oxford University Press (OUP)
- Published
- 2023-08-19
- Volume
- 28
- Issue
- 12
- Pages
- e1209-e1218
- ISSN
- 1083-7159 (ISSN-L)
- 1549-490X
- PMC
- PMC10712701
- OpenAlex
- W4386002127
- Cited by
- 3
- References
- 29
- Citations by year
- 2025: 2 · 2024: 1
- FWCI
- 0.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- The Oncologist (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Lirias (submittedVersion, cc-by)
- Funders
- Array Biopharma in collaboration with Novartis
- National Institutes of Health Cancer Center (P30 CA 008748)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- binimetinib, MEK162, panitumumab, metastatic colorectal cancer, RAS mutations, BRAF wild-type, EGFR inhibition, MEK inhibition, combination therapy, dose escalation, treatment toxicity, diarrhea, acneiform dermatitis
- MeSH terms
- Panitumumab, Antineoplastic Combined Chemotherapy Protocols, Benzimidazoles, Colonic Neoplasms, Humans, Rectal Neoplasms, Colorectal Neoplasms, Proto-Oncogene Proteins p21(ras), ErbB Receptors
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