In line with this, recent Phase 1 studies in BRAFV600E-CRC have reported that addition of the topoisomerase inhibitor irinotecan to BRAFi + MEKi combination increased activity55 (ORR of 35% compared to 12%) (ref. 16), as did the PI3K inhibitor alpelisib to BRAFi + EGFRi treatment56 (ORR of 18% compared to 4% (ref. 14) or 17% (ref. 36) for the doublet). This evidence concerns the gene PIK3CA and colorectal carcinoma.