Apalutamide on the PBS

The Pharmaceutical Benefits Scheme (PBS) listing for apalutamide has been expanded to include metastatic castration-sensitive prostate cancer. Apalutamide is an androgen receptor inhibitor. It can reduce tumour volume by decreasing tumour cell proliferation and increasing apoptosis.

The efficacy of apalutamide in patients with metastatic castration-sensitive prostate cancer was investigated in the TITAN trial. In this double-blind study, patients were randomised to receive apalutamide or a placebo, in addition to androgen deprivation therapy. Radiographic progression-free survival at 24 months was significantly longer in the apalutamide group compared to placebo (68.2% vs 47.5%). Overall survival was also significantly longer in the apalutamide group (82.4% vs 73.5%) at 24 months. The side effect profile was similar in the two groups, although apalutamide was associated with a higher incidence of rash, hypothyroidism, and ischaemic heart disease.

Apalutamide may induce the drug metabolising enzymes, UDP-glucuronosyl transferase (UGT). These enzymes also metabolise thyroid hormones, which may increase the risk of hypothyroidism. Patients already prescribed thyroid replacement therapy may require dose adjustment. Apalutamide can also cause drug interactions due to its effect on other drug metabolising enzymes. It is a strong inducer of CYP2C19 and CYP3A4, a weak inducer of CYP2C9, and is predominantly metabolised by CYP2C8 and CYP3A4.

The usual apalutamide dose is 240mg orally daily. It should be given in conjunction with a gonadotropin-releasing hormone (GnRH) analogue unless the patient has had a bilateral orchiectomy.