Encorafenib

UK SPC (Braftovi 50 mg hard capsules, https://www.medicines.org.uk/emc/product/9499/smpc). Treatment should be initiated and supervised under the responsibility of a physician experienced in the use of anticancer medicinal products. PATIENT SELECTION: BRAF V600E mutation must be confirmed with a CE-marked in vitro diagnostic device (or an alternative validated test) before starting; efficacy and safety have been established only in melanoma with BRAF V600E/V600K mutations, colorectal tumours with BRAF V600E, and NSCLC with BRAF V600E. Encorafenib should not be used in wild-type BRAF melanoma, colorectal cancer or NSCLC. ADMINISTRATION: capsules are swallowed whole with water, with or without food; avoid concomitant grapefruit juice; for patients unable to swallow, capsules may be opened and the contents dispersed in approximately 20 mL of apple sauce and taken immediately. Missed dose: only take it if it is more than 12 hours until the next scheduled dose. Vomiting after a dose: do not take an additional dose, take the next scheduled dose. DOSE REDUCTIONS (melanoma/NSCLC with binimetinib): starting 450 mg once daily -> 1st reduction 300 mg once daily -> 2nd reduction 225 mg once daily; for melanoma there are limited data for reduction to 100 mg once daily and encorafenib should be permanently discontinued if 100 mg once daily is not tolerated; for NSCLC, permanently discontinue if 225 mg once daily is not tolerated. Administration of 450 mg once daily as a SINGLE AGENT is not recommended - if binimetinib is temporarily interrupted, reduce encorafenib to 300 mg once daily during the interruption; if binimetinib is permanently discontinued, discontinue encorafenib; if encorafenib is interrupted or discontinued, binimetinib should be interrupted or discontinued correspondingly. DOSE REDUCTIONS (colorectal cancer with cetuximab, or cetuximab plus FOLFOX): starting 300 mg once daily -> 1st reduction 225 mg once daily -> 2nd reduction 150 mg once daily; permanently discontinue if 150 mg once daily is not tolerated. If encorafenib is permanently discontinued, cetuximab should be discontinued (FOLFOX alone may continue per standard of care); if cetuximab is permanently discontinued, encorafenib should be discontinued; if FOLFOX is permanently discontinued, encorafenib plus cetuximab may continue. TOXICITY MODIFICATIONS (SPC Tables 3 and 4) cover cutaneous reactions, palmar-plantar erythrodysaesthesia syndrome, uveitis/iritis/iridocyclitis, QTc prolongation (withhold and reduce for QTcF >500 ms with change <=60 ms from baseline; permanently discontinue for QTcF >500 ms increased by >60 ms from baseline), and liver laboratory abnormalities; recurrent or intolerable Grade 2 and first Grade 3 or 4 reactions - withhold for up to 4 weeks then resume at a reduced dose if improved to Grade 0-1 or baseline, otherwise permanently discontinue. No dose modification is required for new primary cutaneous malignancies; consider permanent discontinuation for new primary non-cutaneous RAS mutation-positive malignancies. Elderly: no dose adjustment for patients aged 65 years and older. Hepatic impairment: administer with caution at 300 mg once daily in mild impairment (Child-Pugh A); no dosing recommendation can be made in moderate (Child-Pugh B) or severe (Child-Pugh C) impairment. PAEDIATRIC: safety and efficacy have not yet been established in children and adolescents, no data available. Any under-18 use must be verified against a children's formulary and specialist paediatric oncology protocol.