Quality of life with first-line EC+mFOLFOX6 in BRAF V600E-mutant mCRC

In this video, Prof Dr Eric Van Cutsem speaks with Dr Sara Lonardi about patient-reported quality-of-life (QoL) outcomes from the phase III BREAKWATER study, presented at ESMO GI 2026.¹ BREAKWATER evaluated first-line encorafenib plus cetuximab (EC) and mFOLFOX6 versus standard chemotherapy with or without bevacizumab in patients with previously untreated BRAF V600E-mutant metastatic colorectal cancer (mCRC). While the primary aim of BREAKWATER was to demonstrate efficacy, Prof Dr Lonardi emphasises that maintaining QoL is essential, particularly when treatment intensification may increase toxicity.

The analysis showed that adding EC to mFOLFOX6 did not lead to clinically meaningful deterioration in global health status, physical functioning or role functioning. Although the experimental regimen was associated with somewhat more toxicity, overall QoL remained comparable between treatment arms. Some symptom scores, including pain and diarrhoea, numerically favoured EC+mFOLFOX6. 

Prof Dr Lonardi notes that this is clinically relevant because patients receiving EC+mFOLFOX6 live longer and remain on treatment for longer. The poster focused on the mFOLFOX6 backbone, but similar QoL findings were observed with EC+FOLFIRI and will be included in the manuscript. For older or frailer patients who are not candidates for combination chemotherapy, EC without chemotherapy may be considered in selected cases, although this would remain off-label in the first-line setting. Overall, these data further support EC+mFOLFOX6 as a practice-changing first-line option for eligible patients with BRAF V600E-mutant mCRC.