Dr Kopetz on the Investigation of Encorafenib, Cetuximab, and Chemotherapy in mCRC

Scott Kopetz, MD, PhD, FACP, professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the phase 3 BREAKWATER trial (NCT04607421) in patients with BRAF V600E–mutant metastatic colorectal cancer (mCRC).

The phase 3 trial evaluated encorafenib (Braftovi) plus cetuximab (Erbitux) with or without mFOLFOX6 or FOLFIRI vs chemotherapy alone in this patient population. Kopetz shares that the trial investigators are encouraged by the response rates that were reported, adding that biomarker findings were integrated into the data as well. One emerging biomarker is circulating tumor DNA (ctDNA), Kopetz says. In patients with BRAF V600E mutations, investigators can measure BRAF V600E–mutated ctDNA and track how it changes with treatment, he explains.

Most patients in the phase 3 trial who received chemotherapy combined with encorafenib and cetuximab had complete clearance of their BRAF V600E–mutant ctDNA, Kopetz emphasizes. Although this is an encouraging sign of efficacy, it does not mean that these tumors are completely eradicated, but rather that the amount of disease has been driven below the limits of detection.

Overall, the BREAKWATER investigators are excited by both the safety and efficacy data, Kopetz continues, adding that the BRAF V600E–mutant mCRC population needs new and innovative treatment strategies. Further research and new therapeutic approaches, such as bringing targeted therapies into earlier lines of therapy, may improve outcomes for these patients, Kopetz explains. Moreover, by combining these new approaches with cytotoxic chemotherapy, investigators may harness some of the biological synergy between these combinations, Kopetz adds. Overall, these new approaches are anticipated to improve responses, progression-free survival, and ultimately, overall survival for this population, he concludes.