Although anti-CTLA4 + anti-PD1 clearly provides superior OS benefit in advanced melanoma compared with anti-PD1 alone [39,79], it is still unclear whether a pure immune modulatory drug such as anti-CTLA4 is better than a supposedly anti-cancer drug, such as BRAF/MEK inhibitor, when combined with anti-PD(L)1 for the treatment of advanced melanoma [80]. The gene discussed is CTLA4; the disease is melanoma.