What if Prostate Specific Antigen (PSA) levels decline only slightly 30 days after starting Androgen Deprivation Therapy (ADT) plus apalutamide?

From the Guidelines

If PSA levels decline only slightly 30 days after starting ADT plus apalutamide, it is crucial to promptly re-evaluate the treatment strategy, as this may indicate a suboptimal response to therapy, and consider alternative approaches to improve outcomes, as evidenced by the TITAN clinical trial 1. When considering the management of patients with metastatic, castration-sensitive prostate cancer, the addition of apalutamide to ADT has been shown to significantly improve radiographic progression-free survival and overall survival, with a maintained health-related quality of life 1.

• Key points to consider in this scenario include:
  • The patient's PSA response, although slight, should be evaluated in the context of their overall clinical picture, including symptoms, performance status, and imaging findings.
  • The TITAN trial demonstrated the efficacy of apalutamide in combination with ADT, with a significant improvement in median overall survival compared to ADT alone, after a median follow-up of 44 months 1.
  • Potential next steps may include:
    • Additional testing, such as imaging studies, to assess disease progression or treatment resistance.
    • Consideration of treatment modifications, including the addition of other agents or exploration of clinical trials.
    • Regular PSA monitoring to assess the patient's response to therapy and adjust the treatment plan as needed.
• It is essential to note that individual responses to therapy can vary, and some patients may experience delayed PSA responses, emphasizing the importance of comprehensive clinical evaluation rather than reliance on PSA values alone.
• The current standard dose of apalutamide is 240mg daily, and any modifications to the treatment plan should be made in consultation with an oncologist, taking into account the patient's specific clinical context and the latest evidence-based guidelines, such as those outlined in the NCCN clinical practice guidelines in oncology 1.

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 specific guidance on what to do if PSA levels decline only slightly 30 days after starting ADT plus apalutamide.

• The label reports the percentage of patients who achieved undetectable PSA levels, but it does not address the scenario where PSA levels decline only slightly.
• No conclusion can be drawn from the available data regarding the optimal course of action in this scenario 2.

From the Research

PSA Decline After Starting ADT Plus Apalutamide

• A slight decline in Prostate Specific Antigen (PSA) levels 30 days after starting Androgen Deprivation Therapy (ADT) plus apalutamide may not be entirely indicative of the treatment's effectiveness, as PSA decline can vary among patients 3, 4.
• Studies have shown that deep PSA responses, defined as a ≥90% decline in PSA, are associated with improved clinical outcomes, including longer overall survival and radiographic progression-free survival 3, 4, 5, 6.
• The attainment of early, deep PSA response in metastatic castration-sensitive prostate cancer is an important indicator of treatment effectiveness, and apalutamide has been shown to achieve this response more frequently and earlier than enzalutamide 6.
• A comparison of patients initiated on apalutamide or enzalutamide showed that apalutamide was associated with a significantly higher likelihood of achieving ≥90% reduction in PSA, and this response was observed to occur earlier with apalutamide treatment than with enzalutamide 6.

Factors Influencing PSA Decline

• The rate and extent of PSA decline can be influenced by various factors, including the specific treatment regimen, patient characteristics, and disease severity 3, 4, 5.
• The combination of ADT with apalutamide has been shown to produce rapid, deep, and durable PSA responses in patients with metastatic hormone-sensitive prostate cancer, which are associated with improved clinical outcomes 3, 4, 5.
• The addition of docetaxel to ADT and enzalutamide has also been shown to improve PSA responses and overall survival in patients with metastatic hormone-sensitive prostate cancer 7.

Clinical Implications

• The slight decline in PSA levels 30 days after starting ADT plus apalutamide may not be a cause for concern, as PSA responses can vary among patients and may take longer to develop 3, 4.
• Continued monitoring of PSA levels and clinical outcomes is necessary to assess the effectiveness of the treatment regimen and make any necessary adjustments 3, 4, 5, 6, 7.