Fewer cetuximab-related skin-toxicities in colorectal cancer patients treated with encorafenib: a Yin and Yang effect of ERK paradoxical activation

Cetuximab is a biotherapy targeting EGFR in KRAS and NRAS wild-type colorectal tumors. Cetuximab-related side-effects are mostly skin toxicities, including severe forms such as skin rash, skin dryness, pruritus, paronychia, hair abnormality, and mucositis. The pharmacokinetic parameters of cetuximab are associated with clinical outcome in patients with colorectal cancer.1 As exposure–effects relationships apply to both efficacy and safety, toxicities could be a marker for treatment efficacy—a concept coined as the ‘No pain, no gain’ paradigm.