Table 3.

Management of Common Adverse Events Related to BRAF and MEK Inhibitors

Adverse Event	Management Recommendations
Rash	Implement preventive measures when initiating therapy: avoid excessive sunlight, apply sunscreen daily, topical mild steroid (eg, hydrocortisone 1% cream) or topical antibiotic (eg, clindamycin cream) applied 2×/d. Consider oral antibiotics (eg, doxycycline 100 mg 2×/d or minocycline 100 mg 2×/d). If no improvement within 2 wk, consider holding MEKi until rash improves and then resuming at a reduced dose.
Diarrhea	Institute supportive care (dietary modification, hydration, loperamide). Continue BRAFi/MEKi for uncomplicated diarrhea, but consider holding both medications for grade ≥ 2 diarrhea that continues > 48 h, or complicated diarrhea.
Nausea/Vomiting	Promptly institute antiemetic measures. If AE is grade 1 to 2, can generally continue BRAFi/MEKi, but if higher grade should hold BRAFi and MEKi until symptoms improve.
Vision change	If AE is grade 1, continue drugs while obtaining ophthalmology consultation within 1 wk. If grade ≥ 2, obtain urgent consult and hold MEKi. Dose modification or discontinuation depends on diagnosis (uveitis, serous neuroretinal detachment, or retinal vein occlusion).
Fevers	Clinical evaluation and workup for infection. Implement antipyretics at first occurrence (acetaminophen, ibuprofen, etc). Hydration as required. Consider oral corticosteroids (eg, dexamethasone 2 mg for 5 d). Consider dose reduction of BRAFi.
Left ventricular function, decreased	Hold MEKi and reevaluate LVEF closely. Consider resuming MEKi at a reduced dose if LVEF improves; otherwise discontinue.
Liver enzyme elevation	Continue BRAFi/MEKi for asymptomatic patients with mild elevation and observe closely for improvement. If grade 3 to 4, hold BRAFi and MEKi, consider workup for other etiologies of liver injury, and resume drugs at a reduced dose if patient improves to grade ≤ 1.
Interstitial lung disease	For AE grade ≥ 2, hold MEKi while pursuing workup (consider chest CT, pulmonary function tests, infection workup, pulmonology consult). Consider symptomatic therapy with corticosteroids and resume MEKi at a reduced dose if AE improves to grade ≤ 1.

Abbreviations: AE, adverse event; BRAFi, BRAF inhibitor; LVEF, left ventricular ejection fraction; MEK, mitogen-activated protein kinase kinase; MEKi, MEK inhibitor.