An open-label large phase 1 study has recently evaluated the triple combination of BRAF/MEK/EGFR inhibitors (as shown in Fig. 1c) in 142 patients with BRAF-mt CRC, and shows promising results (confirmed response rates of 21%) with an acceptable safety profile, with mostly dermatological toxicity.51 However, further randomised studies are required for a number of reasons: first, to find the most effective combination; second, to improve the tolerability of these combination therapies; and third, to compare them with standard chemotherapeutic regimens. Here, BRAF is linked to colorectal carcinoma.