BRAFTOVI

What it is

BRAFTOVI (encorafenib) is supplied as hard capsules in two strengths: 50 mg and 75 mg.

Approved indications

— Treatment of adult patients who have unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by a validated test, in combination with binimetinib. — Treatment of adult patients who have metastatic colorectal cancer with a BRAF V600E mutation, as detected by a validated test, and who have received prior systemic therapy, in combination with cetuximab. — Treatment of adult patients with metastatic non-small cell lung cancer with a BRAF V600E mutation, in combination with binimetinib.

Dosing overview

Encorafenib capsules should be swallowed whole with water, with or without food. Treatment should continue until the patient no longer derives benefit or unacceptable toxicity develops.

Key safety warnings

Haemorrhages, including major haemorrhagic events, can occur with encorafenib. The risk of haemorrhage may be increased with concomitant use of anticoagulant and antiplatelet therapy. Cutaneous malignancies such as cutaneous squamous cell carcinoma including kerathoacanthoma have been observed in patients treated with BRAF inhibitors including encorafenib. New primary melanoma has also been observed. Dermatological evaluations should be performed prior to initiation of therapy with encorafenib, every 2 months while on therapy, and for up to 6 months following treatment discontinuation. QT prolongation has been observed in patients treated with BRAF inhibitors. Encorafenib may cause mild increases in heart rate and small increases in QTc interval. An electrocardiogram (ECG) should be performed before initiation of encorafenib, one month after initiation, and then at approximately 3-month intervals or more frequently, as clinically indicated, while on treatment. Left ventricular dysfunction (LVD), defined as symptomatic or asymptomatic decreases in ejection fraction, has been reported when encorafenib is used in combination with binimetinib. Left ventricular ejection fraction (LVEF) should be assessed by echocardiogram or multi-gated acquisition (MUGA) scan before initiating encorafenib in combination with binimetinib, one month after initiation and then at approximately 3-month intervals or more frequently as clinically indicated while on treatment. Ocular toxicities including uveitis, iritis and iridocyclitis can occur when encorafenib is administered. Patients should be assessed at each visit for symptoms of new or worsening visual disturbances. If symptoms of new or worsening visual disturbances including diminished central vision, blurred vision or loss of vision are identified, a prompt ophthalmological examination is recommended. Creatinine elevation has been commonly reported with encorafenib as single agent or in combination with binimetinib or cetuximab. Observed cases of renal failure including acute kidney injury and renal impairment were generally associated with vomiting and dehydration.

Contraindications

Hypersensitivity to the active substance encorafenib or to any of the excipients.

PBS listing

The 75 mg capsule strength is listed on the PBS with 4 items under streamlined restriction at an ex-manufacturer price of A$1675.18. The 50 mg capsule strength is listed on the PBS with 2 items under streamlined restriction at an ex-manufacturer price of A$763.61.

Regulatory history

BRAFTOVI was first registered on the ARTG on 3 January 2019, with both the 50 mg and 75 mg capsule strengths listed under licence category RE. In November 2018, the PBAC recommended BRAFTOVI for BRAF V600 mutation positive unresectable Stage III or Stage IV metastatic melanoma with streamlined authority required listing. In March 2021, the PBAC deferred consideration of encorafenib for colorectal cancer. Following MSAC support for BRAF V600 testing amendments, the PBAC recommended listing in May 2021 for metastatic (Stage IV) colorectal cancer (mCRC) with BRAF V600E-variant. The PBAC acknowledged high clinical need, meaningful clinical benefit, and considered the economic model reliable, with acceptable cost-effectiveness and financial impact.