For a metastatic castration‑resistant prostate cancer patient switching from abiraterone acetate to enzalutamide, should the low‑dose prednisolone be stopped?

Should Prednisolone Be Stopped When Switching from Abiraterone to Enzalutamide?

Yes, prednisolone should be stopped when switching from abiraterone to enzalutamide, as enzalutamide does not require concurrent corticosteroid administration and the prednisolone was specifically prescribed to prevent mineralocorticoid excess caused by abiraterone's mechanism of action. 1, 2

Rationale for Stopping Prednisolone

Mechanism-Based Requirement for Abiraterone Only

• Abiraterone irreversibly inhibits CYP17A1, causing predictable upstream accumulation of mineralocorticoids that leads to hypertension (22% of patients), hypokalemia (17%), and peripheral edema (28%) 1, 2
• The concurrent prednisone 5 mg twice daily (or prednisolone equivalent) functions as glucocorticoid replacement therapy to suppress ACTH and reduce mineralocorticoid production, thereby preventing these adverse effects 2, 3
• This corticosteroid is not providing anti-tumor activity but rather compensating for abiraterone-induced cortisol reduction 3

Enzalutamide Does Not Cause Mineralocorticoid Excess

• Enzalutamide works through androgen receptor antagonism and does not inhibit CYP17A1, therefore it does not cause mineralocorticoid excess 1
• No corticosteroid co-administration is required or recommended with enzalutamide monotherapy 1, 4
• The pivotal enzalutamide trials (PREVAIL, AFFIRM) did not include mandatory corticosteroid use 1

Clinical Evidence for Sequential Therapy

Cross-Resistance and Treatment Sequencing

• The Canadian phase 2 crossover trial (n=202) demonstrated that enzalutamide retains activity after abiraterone progression, with 36% of patients achieving PSA responses when enzalutamide was used second-line 5
• Time to second PSA progression was significantly longer with abiraterone-first followed by enzalutamide (19.3 months) compared to the reverse sequence (15.2 months; HR 0.66, p=0.036) 5
• A European single-arm study of 214 patients who progressed on abiraterone plus prednisone for ≥24 weeks showed median radiographic progression-free survival of 8.1 months on subsequent enzalutamide, with 27% achieving PSA responses 4

Safety Profile After Switching

• In the sequential therapy studies, patients who switched from abiraterone to enzalutamide experienced typical enzalutamide-related adverse events (fatigue 32%, decreased appetite 25%, asthenia 18%) without mineralocorticoid excess 4
• No patients were maintained on corticosteroids after switching to enzalutamide in these trials 4, 5

Practical Implementation

Timing of Prednisolone Discontinuation

• Stop prednisolone on the same day you initiate enzalutamide 1, 2
• There is no need for a corticosteroid taper when stopping the low-dose prednisone 5 mg twice daily (or prednisolone 5 mg twice daily) used with abiraterone, as this dose serves as physiologic replacement rather than pharmacologic suppression 3

Monitoring After the Switch

• Monitor blood pressure during the first month after stopping prednisolone, as withdrawal of corticosteroid may unmask any residual mineralocorticoid effects, though this is unlikely once abiraterone is discontinued 1, 2
• Continue standard enzalutamide monitoring for fatigue, hypertension (which can occur with enzalutamide itself in 22% of patients), and seizure risk 1, 4

Critical Pitfall to Avoid

• Do not continue prednisolone "just in case" or for perceived anti-tumor benefit - the modest therapeutic benefit of corticosteroids alone in mCRPC does not justify ongoing exposure to glucocorticoid-related adverse events (bone loss, immunosuppression, hyperglycemia, myopathy) when the primary indication (mineralocorticoid excess prevention) no longer exists 3, 6
• The corticosteroid-related adverse event rate in abiraterone trials was 25.5%, emphasizing that even low-dose prednisone carries risks that should be avoided when no longer indicated 6