Binimetinib

INDICATION AND COMBINATION: binimetinib is given in combination with encorafenib and should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. BRAF V600E mutation must be confirmed by a CE-marked in vitro diagnostic (or an alternative validated test) before starting; efficacy and safety are established only in melanoma expressing BRAF V600E/V600K, or NSCLC expressing BRAF V600E. Do not use in wild-type BRAF melanoma or wild-type BRAF NSCLC. DOSE REDUCTION: for patients on 45 mg twice daily the recommended reduced dose is 30 mg twice daily; reduction below 30 mg twice daily is not recommended and therapy should be discontinued if the patient cannot tolerate 30 mg orally twice daily. Re-escalation to 45 mg twice daily may be considered if the adverse reaction is under effective management, but is NOT recommended if the reduction was due to left ventricular dysfunction or any Grade 4 toxicity. COMBINATION HANDLING: if treatment-related toxicities occur, both medicines should be simultaneously dose reduced, interrupted or discontinued — except palmar-plantar erythrodysaesthesia syndrome, uveitis (including iritis and iridocyclitis) and QTc prolongation, where only encorafenib is reduced (see the encorafenib SmPC). If binimetinib is temporarily interrupted, encorafenib should be reduced to 300 mg once daily during the interruption; if binimetinib is permanently discontinued, encorafenib should be discontinued. If encorafenib is interrupted or discontinued, binimetinib should be interrupted or discontinued respectively. TOXICITY MODIFICATIONS (SPC Tables 1 and 2) cover cutaneous reactions, ocular events (symptomatic retinal pigment epithelial detachment, retinal vein occlusion — permanent discontinuation), cardiac events (Grade 2 LVEF decrease: withhold up to 4 weeks and resume reduced if LVEF recovers to at or above LLN with absolute decrease from baseline 10% or less; Grade 3 or 4 LVEF decrease or symptomatic left ventricular dysfunction: permanently discontinue), rhabdomyolysis/CK elevation, venous thromboembolism, liver laboratory abnormalities and interstitial lung disease/pneumonitis; Grade 3 or 4 ILD/pneumonitis requires permanent discontinuation. DURATION: continue until the patient no longer derives benefit or unacceptable toxicity develops. MISSED DOSE: do not take if less than 6 hours until the next dose is due. VOMITING: do not re-take the dose; take the next scheduled dose. ELDERLY: no dose adjustment for patients 65 years and older. HEPATIC: no adjustment in mild impairment (Child-Pugh A); binimetinib is not recommended in moderate (Child-Pugh B) or severe (Child-Pugh C) impairment because encorafenib is not recommended in these patients. PAEDIATRIC: the safety and efficacy of binimetinib in children and adolescents have not yet been established; no data are available.