From the Research
Restarting Androgen Deprivation Therapy (ADT) with apalutamide (Erleada) is unlikely to cause a testosterone flare or subsequent increase in PSA levels. Unlike LHRH agonists (such as leuprolide), apalutamide is an androgen receptor inhibitor that does not initially stimulate testosterone production before suppressing it. When restarting ADT, the concern about testosterone flare primarily applies to LHRH agonists used alone without an anti-androgen. Apalutamide works by directly blocking the androgen receptor, preventing testosterone and dihydrotestosterone from binding and activating prostate cancer cells, regardless of circulating testosterone levels.
Key Points to Consider
- The mechanism of action of apalutamide does not involve an initial surge in testosterone levels, which is a key factor in testosterone flare associated with LHRH agonists 1, 2.
- Studies have shown that apalutamide, when used in combination with ADT, leads to significant reductions in PSA levels and improves clinical outcomes in patients with advanced prostate cancer 3, 4.
- The standard dose of apalutamide is 240 mg (four 60 mg tablets) taken orally once daily, and patients should be monitored with regular PSA testing after restarting therapy to ensure the treatment is effective 5.
- If a patient is restarting a complete ADT regimen that includes both an LHRH agonist and apalutamide, it would be prudent to start the apalutamide a few days before the LHRH agonist to prevent any potential flare from the LHRH component.
Clinical Implications
The use of apalutamide in the treatment of advanced prostate cancer has been supported by recent studies, including the TITAN and SPARTAN trials, which demonstrated improved overall survival and metastasis-free survival in patients treated with apalutamide plus ADT compared to ADT alone 2, 4. The expert opinion statement from European clinical practice also highlights the role of apalutamide in the treatment landscape for patients with advanced prostate cancer, emphasizing its use in combination with ADT for patients with metastatic hormone-sensitive prostate cancer and non-metastatic castration-resistant prostate cancer 5.
Monitoring and Management
Patients should be closely monitored for any potential side effects of apalutamide, and regular PSA testing should be performed to assess the effectiveness of the treatment. The management of side effects and the adjustment of the treatment regimen should be individualized based on the patient's response and tolerance to the therapy.