Biomarker-Driven Shifts Signal the Next Generation of mCRC Therapies: With Tanios S. Bekaii-Saab, MD

In today’s episode, we spoke with Tanios S. Bekaii-Saab, MD. Dr Bekaii-Saab is the David F. and Margaret T. Grohne Professor of Novel Therapeutics for Cancer Research I, at the Mayo Clinic College of Medicine and Science, the division chair of Hematology/Medical Oncology at Mayo Clinic, and co-leader of the Advanced Clinical and Translational Science Program and the disease group leader for Gastrointestinal Cancers for the Mayo Clinic Comprehensive Cancer Center in Phoenix, Arizona.
In our exclusive interview, Dr Bekaii-Saab discussed findings from the final analysis of cohort 3 of the phase 3 BREAKWATER trial (NCT04607421), which were presented at the 2026 ASCO Annual Meeting. These data showed that encorafenib (Braftovi) plus cetuximab (Erbitux) and FOLFIRI (leucovorin, 5-fluorouracil, and irinotecan) significantly improved outcomes compared with standard of care in patients with BRAF V600E–mutant metastatic colorectal cancer (mCRC), building on previously reported data from the trial that led to the February 2026 full FDA approval of encorafenib plus cetuximab and modified FOLFOX6 (leucovorin calcium, fluorouracil, and oxaliplatin) for this patient population. He also highlighted promising bispecific agents targeting VEGF and PD-1, as well as the promise of KRAS G12C inhibitors like calderasib (MK-1084) and sotorasib (Lumakras). Finally, he emphasized that minimal residual disease testing is prognostic and potentially predictive, and can aid in personalized mCRC management.