Mechanism of action

BRAFTOVI + cetuximab target the aggressive biology of BRAF ^V600E-mutant mCRC

Dual inhibition of the MAPK pathway with BRAFTOVI in combination with cetuximab increases anti-tumour activity and reduces mechanisms of resistance^1,8

Mechanism of Disease

BRAF mutations persistently activate the MAPK pathway,
which can stimulate tumor cell growth and proliferation.

BRAF Inhibition

BRAFTOVI targets BRAF V600E, which drives persistent MAPK signaling.
BRAFTOVI is a BRAF kinase inhibitor that binds to BRAF V600E.

Reactivation through EGFR

BRAF inhibition alone leads to reactivation
of the MAPK pathway through EGFR.

Dual inhibition of EGFR and BRAF

BRAFTOVI in combination with cetuximab reduces MAPK reactivation
through EGFR-adaptive feedback.

Cetuximab is an antagonistic, monoclonal antibody that binds to EGFR.

Combined EGFR and BRAF inhibition reduces reactivation
of MAPK signaling.

This is a simplified example of the mechanism of action.

^aPreclinical data.
EGFR, epidermal growth factor receptor; MAPK, mitogen-activated protein kinase.

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Study design

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Patient characteristics

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Overall Survival

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This is a simplified example of the mechanism of action.

^aPreclinical data.
EGFR, epidermal growth factor receptor; MAPK, mitogen-activated protein kinase.

EU HealthCare Professionals

This is an international website for BRAFTOVI dedicated to EU Healthcare professionals (outside the UK and ROI).

IMPORTANT: the information on this website is based on the European Summary of Product Characteristics. Prescribing Information and indication may vary per country. You must refer to your country prescribing information. Please be aware we do not take responsibility for accessing such information which may not comply with the regulation or usage in your country.

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I am Healthcare Professional in the EU (outside the UK and ROl) and I have read the information above.

Patients / Non EU HealthCare Professionals

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I am a patient or a Healthcare Professional outside the EU.

REFERENCES: 1. BRAFTOVI Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/braftovi-epar-product-information_en.pdf. Accessed March 2023 2. Cervantes A, Adam R, Roselló S, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(1):10-32. 3. Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E–mutated colorectal cancer. N Engl J Med. 2019;381(17):1632-1643. 4. Safaee Ardekani G, Jafarnejad SM, Tan L, Saeedi A, Li G. The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis. PLoS One. 2012;7(10):e47054. doi: 10.1371/journal.pone.0047054. 5. Dienstmann R, Salazar R, Tabernero J. Molecular subtypes and the evolution of treatment decisions in metastatic colorectal cancer. Am Soc Clin Oncol Educ Book. 2018;38:231-238.6. Kopetz S, Desai J, Chan E, et al. Phase II pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer. J Clin Oncol. 2015;33(34):4032-4038. 7. Erbitux Summary of Product Characteristics. Merck Europe B.V., 2020. 8. Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E–mutated colorectal cancer [protocol]. N Engl J Med. 2019;381(17):1632-1643. 9. Lai E, Pretta A, Impera V, et al. BRAF-mutant colorectal cancer, a different breed evolving. Expert Rev Mol Diagn. 2018;18(6):499-512. 10. Corcoran RB, Ebi H, Turke AB, et al. EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF-mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov. 2012;2(3):227-235. 11. ClinicalTrials.gov. Search results for phase 3 interventional trials of metastatic colorectal cancer with a BRAF mutation. Accessed March 27, 2020 https://clinicaltrials.gov/ct2/results?cond=Metastatic+Colorectal+Cancer&term=BRAF&cntry=&state =&city =&dist=&Search=Search&phas e=2. 12. European Medicines Agency Public Assessment Report (EPAR). Braftovi EMA/CHMP/175534/2020. 13.Tabernero J, Grothey A, Van Cutsem E et al. Encorafenib plus cetuximab as a new standard of care for previously treated BRAF V600E–mutant metastatic colorectal cancer: updated survival results and subgroup analyses from the BEACON study. J Clin Oncol 2021;39:273–284. 14. Henry JT, Johnson B. Current and evolving biomarkers for precision oncology in the management of metastatic colorectal cancer. Chin Clin Oncol 2019;8(5):49. 15. Ducreux M, Chamseddine A, Laurent-Puig P, et al. Molecular targeted therapy of BRAF-mutant colorectal cancer. Ther Adv Med Oncol 2019;11:1–15. 16. Martinelli E, Cremolini C, Mazard T, et al. Real-world first-line treatment of patients with BRAFV600E-mutant metastatic colorectal cancer: the CAPSTAN CRC study. ESMO OPEN. 2022;7(6):100603. 17. Grassi E, Corbelli J, Papiani G, et al. Current Therapeutic Strategies in BRAF-Mutant Metastatic Colorectal Cancer. Front Oncol. 2021;11:601722. 18. Jones JC, Renfro LA, Zhang BY, et al. Non-V600 BRAF Mutations Define a Clinically Distinct Molecular Subtype of Metastatic Colorectal Cancer. J Clin Oncol 2017;35(23):2624–2630. 19. Taieb J, Le Malicot K, Shi Q, et al. Prognostic Value of BRAF and KRAS Mutations in MSI and MSS Stage III Colon Cancer. J Natl Cancer Inst 2017;109(5):djw272. 20. Seligmann JF, Fisher D, Smith CG, et al. Investigating the poor outcomes of BRAF-mutant advanced colorectal cancer: analysis from 2530 patients in randomised clinical trials. Ann Oncol 2017;28(3):562–568.

This is an international website for BRAFTOVI ®. IMPORTANT: the information on this website is based on the European Summary of Product Characteristics . Prescribing Information and indication may vary per country. You must refer to your country prescribing information. Please be aware we do not take responsibility for accessing such information which may not comply with the regulation or usage in your country