Dr. Kim on Treatment for BRAF-Mutant Colon Cancer

Richard Kim, MD, assistant professor of oncology, University of South Florida College of Medicine, medical oncologist, Department of Gastrointestinal Oncology, Moffitt Cancer Center, discusses treatment options for BRAF-mutant colon cancer.

BRAF-mutant colon cancer makes up about 5% to 10% of the patient population, explains Kim. These patients tend to have poor prognosis as well as have right-sided tumors, are female, and are older. The most common BRAF mutation is V600E, which occurs in about 90% of patients with BRAF mutations. Patients with BRAF V600E have a shorter life expectancy at 9 to 14 months compared with patients who have BRAF wild-type at about 2 to 3 years, says Kim. Therefore, there is not much time to treat these patients with fourth- or fifth-line therapy; rather, these patients must receive aggressive treatment in the first- or second-line setting. A more aggressive approach needs to be created for this patient population, states Kim.

In 2019, there are drugs that target the BRAF pathway. A BRAF inhibitor alone seems to have strong efficacy with response rate, overall survival (OS), and progression-free survival (PFS) in other BRAF-mutant cancers. However, single-agent vemurafenib (Zelboraf) used in colon cancer showed a low response rate of less than 5% with modest PFS and OS, according to Kim. This is because blocking BRAF creates a feedback loop that stimulates the EGFR pathway, thereby reactivating the MAP kinase pathway. Therefore, in colon cancer, the BRAF and EGFR pathways must be blocked simultaneously. Treatment can also take it one step further by blocking the MEK pathway, as well, to see if the triplet has more efficacy, concludes Kim.