Would you consider adding encorafenib + cetuximab to adjuvant mFOLFOX for a patient with oligometastatic colon cancer with BRAF V600E mutation s/p metastasectomy and primary resection given the data from the BREAKWATER trial?

This is a compelling question, and I agree with many of the points made by the other respondents. In a patient with metastatic, completely resected BRAF-mutated colon cancer, I would consider using a ctDNA minimal residual disease assay (such as Signatera) to inform decision making. If the patient is ctDNA negative, I would either follow with standard adjuvant therapy or observation (depending on duration of neoadjuvant therapy). If the patient is ctDNA positive, I would consider using FOLFOX + encorafenib + EGFR inhibitor. This is not an evidence-based approach, admittedly.

Great question without clear evidence.

Given the generally poor clinical outcomes for patients with BRAF V600E-mutated metastatic colorectal cancer, metastasectomy is not commonly offered unless the patient shows prolonged disease response/stability on maintenance treatment. We still have very few successful cases, even in this highly selected population. There are no optimal timing/clear criteria for how long the patient should be on maintenance treatment before the metastasectomy, but we would not offer metastasectomy only after a couple of cycles of treatment.

Based on the limited information, I would guess this patient must have great response and stable disease for a prolonged period before the curative intent surgical intervention, th...

While the prognosis for patients with resected stage IV BRAF V600E-mutant colorectal cancer remains poor despite adjuvant FOLFOX, emerging data—such as the significantly higher response rates seen with FOLFOX plus encorafenib and cetuximab in the first-line metastatic setting (as demonstrated in the BREAKWATER trial and now supported by FDA approval)—offer a compelling rationale for considering this triplet earlier in the disease course. Given the patient’s diagnosis of stage IV BRAF V600E-mutant colorectal cancer—even if currently NED post-metastasectomy—the use of encorafenib and cetuximab remains aligned with its approved indication in metastatic disease, particularly in the context of high risk of present micrometastatic disease and rel...