apalutamide

Apalutamide is a non-steroidal antiandrogen (NSAA) used in the treatment of prostate cancer. Marketed as Erleada by Janssen, it is approved for men with nonmetastatic castration-resistant prostate cancer (nmCRPC) and, in combination with ongoing androgen deprivation therapy (ADT), for metastatic castration-sensitive or castration-resistant prostate cancer.

Apalutamide binds to the androgen receptor with high affinity, inhibiting receptor nuclear translocation and DNA binding, thereby blocking androgen-driven transcription. As a second-generation AR antagonist, it provides therapeutic activity in tumors that persist despite castrate testosterone levels.

The drug is taken orally at 240 mg once daily, with or without food, and used together with continuous ADT to maintain castrate testosterone levels (<50 ng/dL). The pharmacokinetics show a long terminal half-life, and active metabolites contribute to exposure.

Key trials include SPARTAN, which showed longer metastasis-free survival in nmCRPC, and TITAN, which demonstrated improved radiographic progression-free survival and overall survival when added to ADT in metastatic hormone-sensitive prostate cancer.

Common adverse effects include fatigue, rash, hot flashes, weight loss, and diarrhea. Rash can be severe; hypothyroidism and increased risk of falls or fractures have been reported. Seizure risk exists but is relatively low; patients with risk factors require monitoring.

Apalutamide is a potent inducer of CYP3A4, CYP2C9, and CYP2C19, reducing plasma levels of many drugs. Caution with medications such as warfarin and certain antiepileptics. Clinicians should review concomitant therapies and adjust as needed.

Approved by the U.S. FDA in 2018 for nmCRPC and in 2020 for mCSPC, apalutamide is available as Erleada. Its labeling emphasizes combination with ADT and monitoring for rash, thyroid function, and seizure risk.