Cobimetinib is associated with diverse, often grade-dependent toxicities requiring proactive management.

Common and Severe Adverse Reactions

Melanoma cohort: Most frequent AEs (≥20%) included diarrhea (60%), photosensitivity (46%), nausea (41%), pyrexia (28%), and vomiting (24%). Grade 3–4 lab abnormalities included elevated GGT (21%), CPK (14%), and lymphopenia (10%). Histiocytic neoplasms: Common AEs included acneiform dermatitis (65%), diarrhea (62%), infections (62%), and fatigue (42%). Severe AEs (grade ≥3) included CPK elevation (27%), hyponatremia (18%), and decreased LVEF (12%). Class-specific risks included hemorrhage (13% melanoma; 19% histiocytosis), retinopathy (26% melanoma), and rhabdomyolysis (3.6% melanoma). Dose interruptions/reductions occurred in 55% of melanoma patients. Fatalities from AEs were rare but linked to hepatotoxicity or cardiomyopathy.