Would you use encorafenib with cetuximab vs encorafenib alone as second line therapy in a patient with metastatic colon cancer with concomitant KRAS G12V and BRAF V600E mutations identified on liquid biopsy?

I would rather state this question as, "Would you use encorafenib with cetuximab or cetuximab with encorafenib plus binimetinib (triplet regimen), or cetuximab in combination with irinotecan based chemotherapy?"

Based on the available data, it seems like KRAS mutation was not relevant. BEACON trial (Kopetz et al., PMID 31566309) enrolled 665 patients with BRAF V600E–mutated metastatic colorectal cancer who had had disease progression after one or two previous regimens and randomly assigned them into encorafenib, binimetinib, and cetuximab (triplet-therapy group); encorafenib and cetuximab (doublet-therapy group); or the investigators’ choice of either cetuximab and irinotecan or cetuximab and FOLFIRI.

Interestingly, in their published article (Kopetz et al., PMID 31566309) authors gave no data regarding the KRAS mutation status of the 665 enrolled patients. On my commentary (letter to editor), I questioned this data (unpublished data). I am still curious to this date, what was the KRAS mutation status of these 665 patients in BEACON trial?

The rationale to use cetuximab was based on the preclinical data showing that BRAF inhibitor treatment alone did not sufficiently inhibit pathway signaling due to rapid EGFR pathway activation, and clinical trials supporting increased antitumor activity of BRAF inhibition when combined with anti-EGFR monoclonal antibodies.

So the question here is, should this patient be given encorafenib+ cetuximab with or without binimetinib in the setting of a truly BRAF mutated colon cancer (agree with confirming BRAF mutation), regardless of KRAS mutation status in liquid or tissue biopsy. I would give a try to triplet regimen if the patient is in good performance status and able to tolerate.

https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf