When to use Orgovyx (relugolix) vs Erleada (apalutamide) in patients with advanced prostate cancer?

When to Use Orgovyx vs Erleada in Advanced Prostate Cancer

Orgovyx (relugolix) should be used as first-line ADT in patients with advanced hormone-sensitive prostate cancer (HSPC), particularly those with cardiovascular risk factors, while Erleada (apalutamide) should be used in combination with ADT for metastatic HSPC or high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) with PSADT ≤10 months.

Disease State Considerations

Hormone-Sensitive Prostate Cancer (HSPC)

• Orgovyx (relugolix):

  • First oral GnRH receptor antagonist for ADT in advanced HSPC 1
  • Provides rapid testosterone suppression without initial testosterone flare 2
  • Superior castration rate compared to leuprolide (96.7% vs 88.8%) 3
  • Significantly lower risk of major cardiovascular events (HR 0.46) 4

• Erleada (apalutamide) + ADT:

  • For metastatic HSPC (mHSPC) in combination with ADT 4
  • Demonstrated significant PFS gain (23.9 months) and OS gain (28.1 months) in TITAN trial 4
  • Strong recommendation (Grade A evidence) for use with ADT in mHSPC 4

Castration-Resistant Prostate Cancer (CRPC)

• Erleada (apalutamide):

  • Category 1, preferred option for non-metastatic CRPC with PSADT ≤10 months 4
  • Improved metastasis-free survival (40.5 vs 16.2 months) in SPARTAN trial 4
  • Improved overall survival (59.9 vs 73.9 months) despite 19% crossover 4
  • Not indicated for metastatic CRPC

• Orgovyx (relugolix):

  • Not specifically indicated for CRPC
  • Similar castration resistance-free survival compared to leuprolide in the HERO trial 5

Clinical Decision Algorithm

1. For initial ADT in advanced prostate cancer:

   • Choose Orgovyx (relugolix) if:
     • Patient has cardiovascular risk factors (54% lower risk of major cardiac events) 3
     • Rapid testosterone suppression is needed (56% castrate levels by day 4 vs 0% with leuprolide) 3
     • Oral administration is preferred or beneficial for the patient
     • Avoiding testosterone flare is important

2. For metastatic hormone-sensitive prostate cancer (mHSPC):

   • Choose Erleada (apalutamide) + ADT if:
     • Patient needs intensification of therapy beyond ADT alone
     • Long-term disease control is priority (OS gain of 28.1 months in TITAN trial) 4
   • Consider Orgovyx as the ADT component when combining with apalutamide
     • Recent data supports safety and efficacy of relugolix + apalutamide combination 6

3. For non-metastatic castration-resistant prostate cancer (nmCRPC):

   • Choose Erleada (apalutamide) if:
     • PSADT ≤10 months (high risk for developing metastatic disease) 4
     • Metastasis-free survival is a priority endpoint

Important Considerations and Caveats

• Cardiovascular risk: Orgovyx has a significantly lower risk of major cardiovascular events compared to traditional LHRH agonists (HR 0.46) 4, making it preferred in patients with cardiovascular comorbidities.

• Administration route: Orgovyx is administered orally once daily, while Erleada is also oral but must be combined with injectable ADT unless using Orgovyx as the ADT component.

• Testosterone recovery: Orgovyx allows faster testosterone recovery after discontinuation (288.4 ng/dL vs 58.6 ng/dL at 90 days) 3, which may be relevant for intermittent therapy or if treatment needs to be discontinued.

• Side effect profiles:

  • Erleada: Rash (24%), fracture (11%), hypothyroidism (8%), ischemic heart disease (4.4%) 4
  • Orgovyx: Similar to other ADT agents but with reduced cardiovascular risk 3

• Combination therapy: Both agents can be used in combination therapies - Erleada with traditional ADT, and emerging data supports Orgovyx in combination with abiraterone or apalutamide 6.

By following this algorithm and considering these factors, clinicians can optimize treatment selection between Orgovyx and Erleada based on disease state, cardiovascular risk, and treatment goals.