Updates in BRAF V600E-Mutated Metastatic Colorectal Cancer

This independent medical education was funded by Pierre Fabre Laboratories, who had no editorial control over the content. This content is not intended for UK Healthcare Professionals.

In this independent medical education webinar, we are joined by Chiara Cremolini, University of Pisa, Italy, and Julien Taieb, Georges Pompidou European Hospital, Université Paris-Cité, France, who discuss the most important updates in BRAF V600E-mutated metastatic colorectal cancer (mCRC) research, including:

• Important treatment advances: 01:08
• Important biomarkers: 02:29
• Aggressive nature of BRAF V600E-mutated mCRC: 04:12
• Importance of early testing and monitoring: 06:30
• MSI-High and MSS tumours: 08:42
• ESMO guidelines: 11:25
• Key clinical trials: 13:23
• Importance of surgery: 18:19
• BRAF as a prognostic marker in resected CRC: 22:22
• Real-world data: 25:02
• The future: 29:27

Read the article for a more in-depth view of the topic.

Key Papers

ESMO guidelines:

Cervantes A et al.; ESMO Guidelines Committee. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(1):10-32.

BEACON CRC trial:
Van Cutsem E et al. Binimetinib, encorafenib, and cetuximab triplet therapy for patients with BRAF V600E-mutant metastatic colorectal cancer: safety lead-in results from the Phase III BEACON Colorectal Cancer Study. J Clin Oncol. 2019;37(17):1460-9.

Taieb’s paper on AEs in BEACON CRC:
Taieb J et al. Adverse events associated with encorafenib plus cetuximab in patients with BRAFV600E-mutant metastatic colorectal cancer: an in-depth analysis of the BEACON CRC study. Clin Colorectal Cancer. 2023;22(1):59-66.

Clinical trial survival data:
Tabernero J 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(4):273-84.

BRAF as a prognostic marker:
Taieb J et al. Different prognostic values of KRAS exon 2 submutations and BRAF V600E mutation in microsatellite stable (MSS) and unstable (MSI) stage III colon cancer: an ACCENT/IDEA pooled analysis of seven trials. Ann Oncol. 2023;34(11):1025-34.

BREAKWATER study:
Kopetz S et al. BREAKWATER: An open-label, multicenter, randomized, phase 3 study, with a safety lead-in (SLI), of first-line (1L) encorafenib (E) + cetuximab (C) ± chemotherapy (CT) vs standard-of-care (SOC) CT for BRAF V600E-mutant metastatic colorectal cancer (mCRC). Abstract TPS3627. J Clin Oncol. 2023;41(Suppl 16).

Future prospects:
Morris VK et al. SWOG S2107: randomized phase II trial of encorafenib and cetuximab with or without nivolumab for patients with previously treated, microsatellite stable, BRAFV600Emetastatic and/or unresectable colorectal cancer. Abstract TPS234. J Clin Oncol 2024;42(Suppl 3).

Other useful references

• Martinelli E et al. European expert panel consensus on the clinical management of BRAFV600E-mutant metastatic colorectal cancer. Cancer Treat Rev. 2023;115:102541.
• Kopetz S et al. Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Engl J Med. 2019;381(17):1632-43.
• Elez E et al. SEAMARK: Phase II study of first-line encorafenib and cetuximab plus pembrolizumab for MSI-H/dMMR BRAFV600E-mutant mCRC. Future Oncol. 2023 Oct 10. doi: 10.2217/fon-2022-1249. Epub ahead of print. PMID: 37815847.
• Tan L et al. A Phase Ib/II trial of combined BRAF and EGFR inhibition in BRAF V600E positive metastatic colorectal cancer and other cancers: the EVICT (Erlotinib and Vemurafenib In Combination Trial) study. Clin Cancer Res. 2023;29(6):1017-30.