XTANDI

What it is

XTANDI is a soft capsule formulation containing 40 mg of enzalutamide, supplied as white to off-white oblong soft gelatin capsules imprinted with "ENZ" in black ink. Enzalutamide is an androgen receptor signalling inhibitor that blocks the androgen receptor signalling pathway by competitively inhibiting androgen binding to androgen receptors and inhibiting nuclear translocation of these receptors and binding to DNA.

Approved indications

— Treatment of patients with non-metastatic hormone-sensitive prostate cancer with biochemical recurrence at high risk for metastasis. — Treatment of patients with metastatic hormone-sensitive prostate cancer. — Treatment of patients with non-metastatic castration-resistant prostate cancer. — Treatment of patients with metastatic castration-resistant prostate cancer following failure of androgen deprivation therapy in whom chemotherapy is not yet indicated. — Treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel.

Dosing overview

The recommended dose of XTANDI is 160 mg (four 40 mg capsules) as a single oral daily dose. XTANDI can be taken with or without food and should be taken at the same time each day. In patients with castration-resistant prostate cancer or metastatic hormone-sensitive prostate cancer, medical castration with a luteinising hormone-releasing hormone (LHRH) analogue should be continued during treatment in patients not surgically castrated. Patients with non-metastatic hormone-sensitive prostate cancer with high-risk biochemical recurrence may be treated with XTANDI with or without androgen deprivation therapy, and treatment can be suspended if PSA is undetectable after 36 weeks, then reinitiated when PSA increases to ≥2.0 ng/mL for patients with prior radical prostatectomy or ≥5.0 ng/mL for patients with prior primary radiation therapy. If a patient experiences Grade 3 or higher toxicity or intolerable adverse reaction, dosing should be withheld for one week or until symptoms improve to Grade 2 or lower, then resumed at the same or reduced dose (120 mg or 80 mg) if warranted.

Key safety warnings

Use of enzalutamide has been associated with seizure, and caution should be used in administering XTANDI to patients with a history of seizures or other predisposing factors including underlying brain injury, stroke, primary brain tumours or brain metastases, or alcoholism. XTANDI should be permanently discontinued in patients who develop a seizure during treatment. There have been rare reports of Posterior Reversible Encephalopathy Syndrome (PRES) in patients receiving XTANDI, a rare reversible neurological disorder which can present with rapidly evolving symptoms including seizure, headache, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. In combined data from five randomised clinical trials, falls or injuries related to falls occurred in 12.0% of patients treated with XTANDI compared to 5.5% of patients treated with placebo, and fall-related injuries were more severe in XTANDI-treated patients and included non-pathologic fractures, joint injuries, and haematomas. Hypersensitivity reactions manifested by symptoms including face oedema, tongue oedema, lip oedema, pharyngeal oedema, and rash have been observed with enzalutamide, and patients who experience any symptoms of hypersensitivity should discontinue enzalutamide and promptly seek medical care. In combined data from five randomised placebo-controlled clinical trials, hypertension was reported in 14.2% of patients receiving XTANDI and 7.4% of patients receiving placebo. There have been reports of patients experiencing difficulty swallowing XTANDI, including reports of choking, due to product size, and patients should be advised to swallow the capsules whole with a sufficient amount of water.

Contraindications

XTANDI is contraindicated in patients with known hypersensitivity to enzalutamide or to any of the excipients in the formulation. XTANDI is contraindicated in women who are, or may become, pregnant.

PBS listing

XTANDI 40 mg soft capsules are listed on the PBS with 3 items requiring authority approval, with an ex-manufacturer price of A$3150.63.

Regulatory history

XTANDI enzalutamide 40 mg soft capsule was first registered on the ARTG on 1 July 2014. On 6 November 2015, the TGA approved an extension of indications for the treatment of patients with metastatic castration-resistant prostate cancer who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated. The PBAC recommended the medicine in November 2017 for extension of current listing for metastatic castration-resistant prostate cancer. In March 2021, the PBAC recommended XTANDI for metastatic castration-resistant prostate cancer prior to docetaxel. In March 2022, the PBAC recommended XTANDI for non-metastatic castration-resistant prostate cancer in combination with ongoing androgen-deprivation therapy. In March 2023, the PBAC recommended XTANDI for metastatic hormone-sensitive prostate cancer.