TAFINLAR

What it is

TAFINLAR is a medicine containing the active substance dabrafenib. It is available as hard capsules containing 50 mg or 75 mg of dabrafenib mesilate, and as dispersible tablets containing 10 mg of dabrafenib mesilate.

Approved indications

— Treatment of patients with BRAF V600 mutation positive unresectable Stage III or metastatic (Stage IV) melanoma in combination with trametinib. — Treatment of patients with BRAF V600 mutation positive unresectable Stage III or metastatic (Stage IV) melanoma as monotherapy. — Adjuvant treatment of patients with a BRAF V600 mutation and involvement of the lymph node(s), following complete resection, in combination with trametinib. — Treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with a BRAF V600 mutation and with no satisfactory locoregional treatment options, in combination with trametinib. — Treatment of patients with advanced non-small cell lung cancer (NSCLC) with a BRAF V600 mutation, in combination with trametinib. — Treatment of paediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy, in combination with trametinib. — Treatment of paediatric patients 1 year of age and older with high-grade glioma (HGG) with a BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options, in combination with trametinib.

Dosing overview

The recommended dose of TAFINLAR in adult patients is 150 mg (two 75 mg capsules) taken twice daily, corresponding to a total daily dose of 300 mg, independent of body weight. Paediatric patients weighing at least 26 kg receive weight-based dosing with capsules, while patients from 1 year of age can use dispersible tablets on a weight-based dosing schedule. For unresectable or metastatic melanoma, metastatic NSCLC, or locally advanced or metastatic anaplastic thyroid cancer, treatment continues until disease progression or unacceptable toxicity, while in the adjuvant melanoma setting, treatment is limited to a maximum of 1 year. TAFINLAR should be taken either at least one hour before, or at least two hours after a meal, leaving an interval of approximately 12 hours between doses.

Key safety warnings

Pyrexia was reported in clinical trials with TAFINLAR monotherapy and in combination with trametinib, with increased incidence and severity when used in combination (57% [119/209], 7% Grade 3) compared to monotherapy (33% [69/211], 2% Grade 3) in patients with unresectable or metastatic melanoma. In 1% of patients in clinical trials, serious non-infectious febrile events were identified defined as fever accompanied by severe rigors, dehydration, hypotension and/or acute renal insufficiency, typically within the first month of therapy. Renal failure has been identified in less than 1% of patients treated with TAFINLAR as monotherapy, but was reported in 7% of patients who received the combination dose of TAFINLAR 150 mg twice daily and MEKINIST 2 mg once daily, with cases generally associated with pyrexia and dehydration that responded well to dose interruption and supportive measures. Cases of cutaneous squamous cell carcinoma (cuSCC) have been reported in patients treated with TAFINLAR as monotherapy (10% [22/211] with median time to onset of approximately 8 weeks) and in combination with MEKINIST (3% [6/209] with median time to onset of 20 to 32 weeks). Skin examination for cuSCC should be performed prior to initiation of TAFINLAR and every month throughout treatment and for up to six months after treatment, with monitoring continuing every two or three months for six months following discontinuation. Cases of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported during treatment with TAFINLAR in combination with trametinib, and patients should be advised of the signs and symptoms and monitored closely for skin reactions, with TAFINLAR and trametinib withdrawn if signs suggestive of SCARs appear. Haemophagocytic lymphohistiocytosis (HLH) has been observed in post-marketing experience with TAFINLAR in combination with MEKINIST, and if HLH is suspected, treatment should be interrupted, with discontinuation and appropriate management if HLH is confirmed. Cases of tumour lysis syndrome, including fatal cases, have been reported in patients treated with TAFINLAR in combination with MEKINIST, and patients with risk factors for tumour lysis syndrome should be closely monitored with prophylaxis considered.

Contraindications

TAFINLAR is contraindicated in patients with hypersensitivity to the active substance dabrafenib mesilate or any of the excipients.

PBS listing

TAFINLAR is registered on the ARTG as 50 mg capsules (ARTG 200922), 75 mg capsules (ARTG 200936), and 10 mg dispersible tablets (ARTG 397093). PBAC recommended the medicine for PBS listing in November 2014 for unresectable or metastatic melanoma with BRAF V600 mutation, with amendments to restriction levels in November 2015 from Authority Required (telephone) to streamlined Authority, followed by recommendations in November 2017 for combination use with trametinib and adjuvant treatment, July 2019 for adjuvant treatment of completely resected Stage IIIB, IIIC or IIID melanoma, March 2024 for paediatric glioma, and March 2025 for adult NSCLC.

Regulatory history

TAFINLAR was approved by the TGA on 21 August 2013 for the treatment of patients with BRAF V600 mutation positive unresectable Stage III or metastatic (Stage IV) melanoma. This medicinal product is subject to additional monitoring in Australia due to approval of an extension of indications.