After patients with metastatic colorectal cancer who have a BRAF V600E mutation stop responding to first-line treatment, they have a median survival of only four to six months. These patients now have a new option in a combination therapy consisting of encorafenib (Braftovi®, Array BioPharma) and cetuximab (Erbitux®, Lilly), which was approved by the FDA earlier this month for adults with previously treated BRAF V600E-mutated metastatic colorectal cancer. In this interview with i3 Health, Scott Kopetz, MD, PhD, FACP, principal investigator of the BEACON CRC trial, on which the approval was based, discusses the significance of the approval and the additional research advances taking place in BRAF V600E-mutated colorectal cancer.
What are the greatest challenges of treating patients with BRAF V600E-mutated metastatic colorectal cancer?
Scott Kopetz, MD, PhD, FACP: This is an aggressive subtype of colorectal cancer, and as a result, treatment outcomes for patients with the prior standards of care were not as good as for patients whose tumors did not carry this mutation.
Can you comment on the significance of the FDA's approval of encorafenib/cetuximab in this population?
Dr. Kopetz: This provides a new effective therapeutic option for patients that is based on the solid foundation of preclinical work to determine what makes this tumor grow and what vulnerabilities it may have to targeted therapy.
What should oncologists consider in balancing encorafenib/cetuximab against other treatment options?
Dr. Kopetz: For patients previously treated with a prior line of therapy for metastatic disease, the targeted therapy combination provides improved survival and a favorable toxicity profile compared with a traditional cytotoxic-based regimen.
What additional research needs to be done regarding encorafenib/cetuximab in BRAF V600E-mutated colorectal cancer?
Dr. Kopetz: The next steps are understanding how to combine this targeted therapy regimen with traditional chemotherapy, both in first-line treatment and potentially in the adjuvant setting as well. Additionally, there are ongoing efforts to combine this with immunotherapy and to develop regimens that may address mechanisms of resistance to this cancer subtype.
About Dr. Kopetz
Scott Kopetz, MD, PhD, FACP, is a Professor of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston. His research interests include the biology of refractory colorectal cancer and the development of novel therapeutics for molecularly distinct subsets of colorectal cancer patients. He is a Senior Editor for Clinical Cancer Research and is a member of the editorial board for the Journal of Clinical Oncology and JNCI: Journal of the National Cancer Institute. He is Vice Chair for Colon Cancer Research in the NSABP/RTOG cooperative group and is Chair of the Colon Cancer Task force of the National Institutes of Health Gastrointestinal Oncology Steering Committee.
For More Information
Kopetz S, Grothey A, Van Cutsem E, et al (2020). Encorafenib plus cetuximab with or without binimetinib for BRAF V600E-mutant metastatic colorectal cancer: quality-of-life results from a randomized, three-arm, phase III study versus the choice of either irinotecan or FOLFIRI plus cetuximab (BEACON CRC). J Clin Oncol (Gastrointestinal Cancers Symposium Abstracts), 38(suppl_4). Abstract 8. DOI:10.1200/JCO.2020.38.4_suppl.8
Clinicaltrials.gov (2019). Study of encorafenib + cetuximab plus or minus binimetinib vs. irinotecan/cetuximab or infusional 5-fluorouracil (5-FU)/folinic acid (FA)/irinotecan (FOLFIRI)/cetuximab with a safety lead-in of encorafenib + binimetinib + cetuximab in patients with BRAF V600E-mutant metastatic colorectal cancer (BEACON CRC). NLM identifier: NCT02928224.
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.