What Prostate-Specific Antigen (PSA) level can a patient expect in 4 weeks after starting Androgen Deprivation Therapy (ADT) and apalutamide (Erleada), given a doubling of PSA from 0.1 to 0.2 in 30 days?

From the Guidelines

After starting Androgen Deprivation Therapy (ADT) and apalutamide (Erleada), a patient with a rapidly rising PSA (doubling from 0.1 to 0.2 in 30 days) can expect a significant PSA decline within 4 weeks, potentially decreasing to approximately 0.05-0.1 ng/mL, based on the mechanism of action of apalutamide and ADT in suppressing testosterone production and blocking androgen receptors in prostate cancer cells 1. The combination of ADT and apalutamide has been shown to be effective in treating non-metastatic castration-resistant prostate cancer (CRPC), with a significant reduction in the risk of distant metastasis or death, as demonstrated in the SPARTAN trial 1. Key points to consider in this patient's treatment include:

• The rapid PSA doubling time before treatment suggests an aggressive cancer that is likely to be hormone-sensitive, which typically responds well to initial androgen suppression therapy.
• Apalutamide's mechanism of action as an AR inhibitor that binds directly to the ligand-binding domain of the AR, inhibiting AR nuclear translocation, DNA binding, and AR-mediated transcription, supports its use in combination with ADT to effectively suppress tumor growth 1.
• Patients should expect PSA testing at regular intervals (typically every 3-6 months) after initial treatment to monitor response, with a successful response generally indicated by a PSA decline of at least 50% from baseline 1.
• If PSA fails to decline appropriately, additional imaging and treatment modifications may be necessary to ensure optimal management of the patient's prostate cancer.

From the FDA Drug Label

Apalutamide 240 mg daily in addition to ADT in patients with mCSPC (TITAN) reduced PSA to undetectable levels (<0.2 ng/mL) in 68% of patients compared to 32% of patients taking ADT alone. The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of apalutamide have not been fully characterized

The FDA drug label does not provide a specific PSA level that a patient can expect in 4 weeks after starting Androgen Deprivation Therapy (ADT) and apalutamide (Erleada), given a doubling of PSA from 0.1 to 0.2 in 30 days. Key points to consider:

• The label reports the percentage of patients with reduced PSA to undetectable levels, but does not provide information on the expected PSA level at a specific time point.
• The exposure-response relationship and time course of pharmacodynamic response for apalutamide have not been fully characterized 2.

From the Research

PSA Level Expectation

Given the doubling of PSA from 0.1 to 0.2 in 30 days after starting Androgen Deprivation Therapy (ADT) and apalutamide, the expected PSA level in 4 weeks can be estimated based on the available studies.

• The studies 3, 4, 5, 6, 7 demonstrate that apalutamide plus ADT produces rapid, deep, and durable PSA responses in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) and metastatic castration-sensitive prostate cancer (mCSPC).
• By 3 months of apalutamide treatment, a significant proportion of patients achieve a deep PSA decline, with 59% and 51% of apalutamide-treated patients achieving a ≥90% PSA reduction or PSA ≤0.2 ng/ml, respectively 4.
• The median time to PSA nadir, confirmed ≥50% PSA reduction, ≥90% PSA reduction, and PSA ≤0.2 ng/ml were 7.4,1.0,1.9, and 2.8 months, respectively, in the SPARTAN study 3.
• Based on these findings, it is likely that the patient's PSA level will continue to decrease over the next 4 weeks, potentially achieving a deeper PSA decline.

Potential PSA Decline

• Considering the rapid PSA decline observed in the studies, the patient's PSA level may decrease to:
  • ≤0.1 ng/ml or lower, given the observed median time to PSA nadir and ≥90% PSA reduction 3
  • A level consistent with the deep PSA decline observed in the majority of apalutamide-treated patients, potentially ≤0.2 ng/ml or lower 4
• However, individual responses to treatment may vary, and the actual PSA level in 4 weeks cannot be predicted with certainty.

Monitoring PSA Levels

• Regular monitoring of PSA levels is essential to assess the treatment response and adjust the treatment approach as needed 5, 7.
• The association between deep PSA decline and improved outcomes, including longer survival time, highlights the importance of monitoring PSA levels to tailor treatment and improve patient outcomes 4, 7.