Table 2.

Toxicity comparison between three FDA-approved BRAFi + MEKi combinations

CombinationMost common toxicitiesLess common toxicitiesDose schedule
Vemurafenib + cobimetinibRash, diarrhea, nausea, arthralgia, fatigue, photosensitivity, pyrexia, vomiting, serous retinopathy, alopecia, and hyperkeratosis.cuSCC, keratoacanthoma, and Bowen disease.Orally, with or without food. Vemurafenib is twice daily every day. Cobimetinib is once daily on days 1 to 21.
Dabrafenib + trametinibPyrexia, nausea, diarrhea, chills, fatigue, headache, and vomiting.Rash, palmer-plantar erythrodysesthesia, photosensitivity, skin papillomas, cuSCC, keratoacanthomas, and hyperkeratosis.Orally, on an empty stomach. Dabrafenib is twice daily. Trametinib is once daily.
Encorafenib + binimetinibDiarrhea, constipation, vomiting, abdominal pain, asymptomatic CPK increase, and blurred vision.Pruritis, hyperkeratosis, rash, keratosis pilaris, palmoplantar keratoderma, palmer-plantar erythrodysesthesia, dry skin, skin papilloma, maculopapular rash, sunburn, alopecia, photosensitivity, arthralgia, myalgia, extremity pain, decreased appetite, musculoskeletal pain, and decreased weight.Orally, with or without food. Encorafenib is once daily, and binimetinib is twice daily.
  • NOTE: Vemurafenib and combimetinib typically cause more skin toxicities. Dabrafenib and trametinib have more fevers. Encorafenib and binimetinib have more gastrointestinal toxicities.

  • Abbreviations: BRAFi, BRAF inhibitor; CPK, creatine phosphokinase; cuSCC, cutaneous squamous cell carcinoma; MEKi, MEK inhibitor.