Dr Kopetz on the Phase 3 BREAKWATER Trial in Frontline Metastatic CRC

“Importantly, this response rate was associated with a higher duration of response [DOR], both at the median [value] as well as at the 6- and 12-month time points. At both the 6- and 12-month time points, the DOR was more than [double] in the experimental arm [compared with] the control arm.”

Scott Kopetz, MD, PhD, FACP, deputy chair and professor, Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, leader, Department of Cancer Center Support Grant, GI Program, TRACTION Medical Director, Division of Therapeutics Discovery Division, and Associate Vice President for Translational Integration, The University of Texas MD Anderson Cancer Center, discusses findings from the phase 3 BREAKWATER study (NCT04607421) of frontline encorafenib (Braftovi) plus cetuximab (Erbitux) with or without chemotherapy in BRAF V600E–mutated metastatic colorectal cancer (CRC).

BREAKWATER was an open-label, multicenter trial that enrolled patients with BRAF V600E–mutated metastatic CRC who received no prior systemic treatment for metastatic disease and had an ECOG performance status of 0 or 1, among other eligibility criteria. Prior findings from the study led to the December 2024 accelerated approval of encorafenib in combination with cetuximab and mFOLFOX6 for patients with metastatic CRC with a BRAF V600E mutation, as detected by an FDA-approved test.

Updated findings from the study demonstrated that the confirmed overall response rate by blinded independent central review was 60.9% (95% CI, 51.6%-69.5%) among patients who received encorafenib plus cetuximab and mFOLFOX6 (n = 110) vs 40.0% (95% CI, 31.3%-49.3%) in those treated with standard-of-care (SOC) chemotherapy alone (n = 110; OR, 2.443; 95% CI, 1.403-4.253; 1-sided P = .0008), Kopetz says. The estimated median DOR was 13.9 months (95% CI, 8.5-not estimable) vs 11.1 months (95% CI, 6.7-12.7), respectively. Most patients (68.7%) in the investigational arm had a DOR of at least 6 months compared with 34.1% of those in the control arm, and 22.4% vs 11.4% of respective patients had a DOR of at least 12 months.