AFINITOR

What it is

Afinitor contains everolimus and is available in tablet strengths of 0.25 mg, 0.5 mg, 0.75 mg and 1 mg. Additional registered strengths include 2 mg, 2.5 mg, 3 mg, 5 mg and 10 mg tablets in various formulations. Everolimus is a selective immunosuppressive agent and proliferation signal inhibitor.

Approved indications

— Treatment of progressive, unresectable or metastatic, well-differentiated, non-functional neuroendocrine tumours (NET) of gastrointestinal or lung origin in adults.

Key safety warnings

Patients on immunosuppressive regimens including everolimus are at increased risk of developing infections, especially with opportunistic pathogens, and fatal infections and sepsis have been reported. Immunosuppressed patients are vulnerable to polyomavirus infections including BK virus-associated nephropathy and potentially fatal JC virus-associated progressive multifocal leukoencephalopathy. Patients receiving everolimus are at increased risk of developing lymphomas or other malignancies, particularly of the skin, with absolute risk related to the duration and intensity of immunosuppression rather than to the use of a specific agent. Patients should be monitored regularly for skin neoplasms and advised to minimise exposure to ultraviolet light and sunlight, and use appropriate sunscreen. Interstitial lung disease with lung inflammation and fibrosis of non-infectious origin, some fatal, has occurred in patients receiving everolimus, though the condition mostly resolves after discontinuation of everolimus and/or addition of glucocorticoids; however, fatal cases have also occurred. Everolimus increases the risk of new onset diabetes mellitus after transplant and blood glucose concentrations should be monitored closely in patients treated with everolimus. Everolimus can impair wound healing, increasing the occurrence of post-transplant complications such as wound dehiscence, fluid collections and wound infection requiring further surgical attention, with lymphocele being the most frequently reported event in renal transplant recipients.

Contraindications

Everolimus is contraindicated in patients with a known hypersensitivity to everolimus, sirolimus or to any of the excipients.

PBS listing

Afinitor tablets are listed on the PBS in strengths of 2 mg, 2.5 mg, 3 mg, 5 mg and 10 mg, with dispersible formulations available in 2 mg, 3 mg and 5 mg strengths. Restriction types include authority required and streamlined listings, with ex-manufacturer prices ranging from A$318.60 for the 2 mg dispersible tablet to A$1593.40 for the 10 mg tablet.

Regulatory history

Afinitor was first registered on the ARTG in 2009 with 5 mg and 10 mg tablet strengths. Additional strengths were registered subsequently, including 2.5 mg tablets in 2012 and dispersible formulations in 2 mg, 3 mg and 5 mg in 2013. In November 2014, the PBAC recommended listing of everolimus for advanced pancreatic neuroendocrine tumours on the basis of acceptable clinical effectiveness and cost-effectiveness compared to best supportive care. In November 2017, the PBAC recommended approval for treatment of adult patients with advanced, progressive, non-functional neuroendocrine tumours of gastrointestinal or lung origin. In July 2018, the PBAC recommended approval for refractory seizures associated with tuberous sclerosis complex as an Authority Required listing for dispersible tablet form, noting high clinical need. An AusPAR was published on 13 January 2017 for the indication of treatment of progressive, unresectable or metastatic, well-differentiated, non-functional neuroendocrine tumours of gastrointestinal or lung origin in adults.