Target therapy (TT) with encorafenib plus cetuximab is a standard option in patients with BRAFV600E-mutated (mut) pretreated metastatic colorectal cancer (mCRC)....Among RNF43 mutants, TT was associated with longer PFS (7.7 v 3.0 months; P = .002) and higher overall response rate (ORR; 45% v 0%; P = .009) compared with CT....Patients with pMMR/MSS BRAFV600E-mut mCRC achieve benefit from TT versus CT independently of RNF43 mutational status, although a higher magnitude of benefit from TT is observed in RNF43-mut tumors.

In total, 25 patients with BRAF V600E-mutant mCRC, treated with a combination of cetuximab and BRAF inhibitor (dabrafenib, vemurafenib, or encorafenib) with/without trametinib... In terms of treatment regimens, 18 patients were treated with cetuximab and vemurafenib; five were treated with a combination of cetuximab, vemurafenib, and trametinib; one was treated with a combination of cetuximab, dabrafenib, and trametinib; and one was treated with a combination of cetuximab and encorafenib...23 patients had progressed with the combinatorial therapies. Of the eight patients with RNF43 mutant mCRC, seven (87.5%) achieved clinical benefit from targeted therapy...Median PFS was significantly better in RNF43 mutant mCRC (10.18 months versus 3.37 months, p = 0.038)...RNF43 mutations as potential biomarkers, predicting favorable response to EGFR/BRAF inhibitors in BRAF V600E-mutant mCRC.