Patients with metastatic colorectal cancer and a BRAF mutation should be given encorafenib, binimetinib and cetuximab rather than old-fashioned chemotherapy according to MD Anderson scientists announcing the results of a Phase III clinical trial.
In the trial (1), the median overall survival increased from 5.4 months to 9 months. A BRAF mutation occurs in approximately 15% of cases in colorectal cancer. The elements of the research took place simultaneously in more than 200 centres worldwide and the research was led by Professor Scott Kopetz at the MD Anderson Cancer Center in Texas. Researchers felt that this Phase III trial should change the standard of care for Colorectal cancer.
Encorafenib (brand name Braftovi), is a small molecule BRAF inhibitor that targets key enzymes in the MAPK signaling pathway and is already used to treat certain melanoma cancers.
Chris Woollams, former Oxford University Biochemist said, “Frankly, 5-FU which is regularly used for CRC in FOLFOX and FOLFIRI combinations, was given its FDA approval in 1956. It is quite ridiculous that with all the money spent on cancer research, we are still using it as the standard of care in the UK and have hitherto not come up with anything better or more targeted. The MD Anderson team need to be applauded. Interestingly, we know the herb berberine has been shown to correct the AMPK pathway, in several studies (3)".
Kopetz is both a scientist and a doctor, and he is leader of the MD Anderson Colorectal 'Moon Shot' project. This aims, he says, to improve detection, monitoring and treatment of colorectal cancer which has such a poor history of treatment, agreeing with Woollams' comments. Kopetz is particularly looking at how immunotherapy drugs might impact colorectal cancer. He has already shown that another BRAF inhibitor vemurafenib can enhance standard treatments.
Woollams added, "Encorafenib is a BRAF inhibitor used with melanoma; binimetinib is an inhibitor of the MAPK tumour promoting pathway, and cetuximab is and EGFR inhibitor already used in the USA with colorectal cancer. All are really monoclonal antibodies targeting an epi-genetic issue, but modern thinking is to call them immunotherapy drugs, which strictly speaking they aren't. It just makes them sound trendier!
Unfortunately, patients with BRAF and colorectal cancer are often told, in the UK that this cancer is 'very rare' and 'incurable'."
The trial was a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate encorafenib + cetuximab plus or minus binimetinib versus Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab, as controls, in patients with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting.
A Phase 2 trial (an Open-label Study of Encorafenib + Binimetinib) is currently being developed by MD Anderson this time for patients with BRAFV600-mutant Non-small Cell Lung Cancer (NSCLC) (2)
Go to: Colorectal Cancer Overview
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References
- Triplet-targeted therapy improves survival for patients with advanced colorectal cancer and BRAF mutations
- A Phase 2, Open-label Study of Encorafenib + Binimetinib in Patients with BRAFV600-mutant Non-small Cell Lung Cancer
- Berberine as a cancer treatment - https://www.canceractive.com/article/Berberine-as-a-cancer-treatment