Early-Onset BRAF Patients Need Faster Treatment: Cathy Eng, MD, FACP, FASCO

Patients with early-onset, BRAF V600E–mutated metastatic colorectal cancer should receive combination therapy as soon as possible, according to Cathy Eng, MD, FACP, FASCO, David H. Johnson Endowed Chair in Surgical and Medical Oncology and professor of medicine (hematology and oncology) at Vanderbilt. In an interview at the Patient-Centered Oncology Care® (PCOC^®) 2026 conference hosted by The American Journal of Managed Care^® in Nashville, Tennessee, September 24-25, 2026, Eng discussed a post hoc analysis of the phase 3 BREAKWATER (NCT04607421) trial in early-onset patients.

What BREAKWATER Showed

Eng explained that BREAKWATER studied newly diagnosed patients with a BRAF V600E mutation, which occurs in about 9% of patients with metastatic colorectal cancer. The trial compared chemotherapy plus a BRAF inhibitor plus anti-EGFR therapy with standard chemotherapy. She described it as "a very positive study" that "definitely improved overall survival."

The post hoc analysis of the early onset population, however, told a more sobering story. The analysis was not powered specifically for this group, but Eng said, "It was striking that the survival for these patients was actually less overall."

Why Timing Matters

Eng said the finding suggests that early-onset patients, particularly those with the BRAF mutation, "should receive the combination as soon as possible to derive the greatest benefit possible." She stressed that the analysis remains important despite its post hoc design, because prior data have shown that some early-onset patients, especially the very young, fare worse than average-age or elderly patients.

She pointed to studies of the very young population, patients in their 20s and 30s, compared with average-age and older patients. In those studies, overall survival was "surprisingly very, very poor," she said.

"BREAKWATER just kind of makes you rethink about options for our young patients," Eng said. She noted that there is no literature at this time indicating that treatment should differ from that of an average-age patient. Still, clinicians "definitely need to be cognizant of providing them the best treatment possible as soon as possible."