Antitumor efficacy with different treatment combination and sequence in BRAFV600E HT29 tumor xenograft. HT29 cells were injected subcutaneously into the left flanks of nude mice and treated with different combination regimen and in different sequence. A, After 2 weeks (average tumor size 200–400 mm3) mice were treated for 6 weeks with: vehicle, encorafenib, cetuximab, alone and in the combination, FOLFOX or FOLFIRI alone, with encorafenib and in combination with E+C. B, After 2 weeks of s.c. injection, mice were treated with vehicle, FOLFOX + encorafenib (10 mice) and FOLFOX + E+C (10 mice). At the end of 3 weeks of therapy, defined as induction treatment, treated mice were randomized into encorafenib alone or E+C, respectively (maintenance treatment). C, After 2 weeks of s.c. injection, mice were treated with vehicle (10 mice), FOLFOX + E+C (30 mice) for 3 weeks, defined as induction treatment. Subsequently treated mice were randomized into 5-FU alone (10 mice), E+C (10 mice), and 5-FU + E+C (10 mice; maintenance treatment).