Are apalutamide and enzalutamide the same?

Apalutamide and Enzalutamide: Different Medications with Similar Mechanisms

No, apalutamide (Erleada) and enzalutamide (Xtandi) are not the same medication, though they are both androgen receptor inhibitors with similar mechanisms of action used to treat prostate cancer. 1

Chemical Structure and Composition

• Apalutamide has the chemical formula C₂₁H₁₅F₄N₅O₂S with a molecular weight of 477.44 2
• Enzalutamide has the chemical formula C₂₁H₁₆F₄N₄O₂S with a molecular weight of 464.44 3
• Both are androgen receptor inhibitors that bind to the ligand-binding domain of the AR, but they have distinct chemical structures 2, 3

Mechanism of Action

• Both medications work by:
  • Inhibiting androgen receptor (AR) nuclear translocation
  • Inhibiting DNA binding
  • Impeding AR-mediated transcription 2, 3
• Both are more potent than first-generation anti-androgens like bicalutamide 1

FDA Approval and Clinical Use

• Apalutamide (Erleada) was FDA-approved in February 2018 for non-metastatic CRPC 1
• Enzalutamide (Xtandi) received FDA approval for non-metastatic CRPC in July 2018 1
• Both are indicated for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) with PSA doubling time ≤10 months 1

Efficacy in Clinical Trials

• Apalutamide in the SPARTAN trial showed:

  • Metastasis-free survival of 40.5 months vs 16.2 months for placebo 1
  • Overall survival of 73.9 months vs 59.9 months for placebo 1

• Enzalutamide in the PROSPER trial demonstrated:

  • Metastasis-free survival of 36.6 months vs 14.7 months for placebo 1
  • Overall survival of 67.0 months vs 56.3 months for placebo 1

Side Effect Profiles

• Apalutamide common side effects include:

  • Rash (23.8% vs 5.5% with placebo) 4
  • Fatigue (30.4% vs 21.1%) 4
  • Fracture risk (11% vs 6.5%) 1
  • Hypothyroidism (8% vs 2%) 1

• Enzalutamide common side effects include:

  • Fatigue (33% vs 14%) 1
  • Hypertension (12% vs 5%) 1
  • Major cardiovascular events (5% vs 3%) 1
  • Mental impairment disorders (5% vs 2%) 1

Comparative Efficacy

• Network meta-analyses suggest that apalutamide may have slightly better efficacy for metastasis-free survival (HR: 0.91; 95% CI: 0.68-1.22) and overall survival (HR: 0.77; 95% CI: 0.46-1.30) compared to enzalutamide, though the confidence intervals overlap 5
• The Bayesian probability of apalutamide being more effective than enzalutamide was 73.6% for metastasis-free survival and 83.5% for overall survival 5

Cross-Resistance

• Cross-resistance exists between apalutamide and enzalutamide, meaning that if a patient develops resistance to one medication, they may also be resistant to the other 6
• This cross-resistance is mediated through the AKR1C3/AR-V7 axis 6

Clinical Implications

• Both medications are category 1, preferred options for patients with non-metastatic CRPC if PSADT is ≤10 months according to NCCN guidelines 1
• Treatment selection should consider the slightly different side effect profiles and patient-specific factors 1
• No head-to-head clinical trials have directly compared these medications 7, 5

Important Monitoring Considerations

• For both medications, monitor for:
  • Fatigue and cardiovascular effects 1, 4
  • Mental status changes 1, 4
  • Seizure risk (rare but present with both medications) 1, 4
• For apalutamide specifically, monitor for rash and thyroid function 1, 4