LAUSR

A triple drug combination of irinotecan, cetuximab, and vemurafenib appears to be more successful at combating metastatic colorectal cancer for longer periods than irinotecan and cetuximab, according to a Journal of Clinical Oncology (JCO) study.1 Results from the SWOG Cancer Research Network are expected to change the standard of care for patients with metastatic colorectal cancer that includes a mutation in the BRAF gene called V600E. Found in approximately 10% of these cancers, the mutation rarely responds to treatment and leads to a poor prognosis. The study was led by Edmund Scott Kopetz, MD, PhD, FACP, a professor in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, and an expert in BRAF-mutated colorectal cancer. He has previously tested a variety of combination therapies and led the phase 3 BEACON trial, which found that 2 targeted drugs—cetuximab and encorafenib—significantly shrank tumors and extended patients’ lives in comparison with patients who had received standard treatment. These findings were published in 2019 in The New England Journal of Medicine.2 Irinotecan is a traditional chemotherapy drug that kills cancer cells, and cetuximab is a monoclonal antibody– targeted drug that blocks the epidermal growth factor protein. Vemurafenib is a targeted BRAF inhibitor. The combination shuts down a major growth pathway in these aggressive cancers, according to Dr. Kopetz. For the JCO study,1 Dr. Kopetz and his colleagues investigated combination therapies in 106 patients whose metastatic colorectal cancer included the V600E mutation. All had undergone previous chemotherapy and did not respond to treatment. Patients were randomly assigned to 1 of 2 treatment groups: those who received irinotecan and cetuximab and those who received that combination along with the third drug, vemurafenib. Findings showed that patients receiving the triple combination responded better to the drugs at a rate of 17% versus a rate of 4% in the 2-drug combination group. The triple combination group also stayed cancer-free longer. The researchers also found an 87% decline in circulating tumor DNA of the BRAF V600E variant allele frequency in patients who received all 3 drugs and no such decline in circulating tumor DNA in patients on the 2-drug combination. Measuring the presence of circulating tumor DNA through liquid biopsy may be an effective way to measure short-term treatment response, Dr. Kopetz adds.