Can a patient with metastatic prostate cancer take Erleada (apalutamide) instead of Eligard (leuprolide)?

Can a Patient with Metastatic Prostate Cancer Take Erleada (Apalutamide) Instead of Eligard (Leuprolide)?

No, Erleada (apalutamide) cannot replace Eligard (leuprolide) because they serve fundamentally different therapeutic roles—apalutamide is an androgen receptor inhibitor that must be given in combination with ongoing androgen deprivation therapy (ADT), while leuprolide is the ADT itself that maintains castrate testosterone levels. 1

Understanding the Distinct Roles

Leuprolide (Eligard) - The Foundation

• Leuprolide is a gonadotropin-releasing hormone (GnRH) analog that serves as the backbone ADT, maintaining castrate serum testosterone levels (<50 ng/dL) 2
• This medication is required continuously for all patients with metastatic prostate cancer unless they have undergone bilateral orchiectomy 1

Apalutamide (Erleada) - The Add-On Therapy

• Apalutamide is an androgen receptor inhibitor that must be given concurrently with a GnRH analog (like leuprolide) or in patients who have had bilateral orchiectomy 1
• The FDA label explicitly states that "patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy" 1

The Correct Treatment Approach

Patients with metastatic castration-sensitive prostate cancer should receive BOTH leuprolide (or another GnRH analog) AND apalutamide together, not one instead of the other. 2, 1, 3

Evidence for Combination Therapy

• The TITAN trial demonstrated that apalutamide 240 mg daily plus ADT significantly improved overall survival compared to ADT alone in metastatic castration-sensitive prostate cancer (82.4% vs 73.5% at 24 months; HR 0.67, P=0.005) 2, 3
• Radiographic progression-free survival at 24 months was 68.2% with apalutamide plus ADT versus 47.5% with placebo plus ADT (HR 0.48, P<0.001) 2, 3
• The final analysis with 44 months median follow-up confirmed a 35% reduction in risk of death with apalutamide plus ADT (HR 0.65, P<0.0001), and 48% after adjusting for crossover 4

Clinical Algorithm for Treatment Selection

For Metastatic Castration-Sensitive Prostate Cancer:

1. Continue leuprolide (Eligard) as the foundation ADT 1
2. Add apalutamide 240 mg orally once daily to improve survival outcomes 2, 3
3. This combination applies to both de novo metastatic disease and patients who received prior local therapies 2

For Non-Metastatic Castration-Resistant Prostate Cancer:

• If PSA doubling time ≤10 months, continue ADT and add apalutamide 240 mg daily (category 1, preferred option) 2
• Apalutamide improved metastasis-free survival from 16.2 to 40.5 months (HR 0.28, P<0.001) 2

Important Safety Considerations

Common Adverse Events to Monitor:

• Fatigue (30.4%), hypertension (24.8%), rash (23.8%), diarrhea (20.3%), and weight loss (16.1%) 2, 5
• Falls (15.6%), fractures (11.7%), and hypothyroidism (8.1%) require specific monitoring 2, 5
• Mental impairment disorders (5.1%) and dizziness (9.3%) warrant neurological assessment 2, 5

Critical Warnings:

• Cardiovascular events: Monitor for cerebrovascular and ischemic heart disease; optimize cardiovascular risk factors 1
• Seizure risk (0.2%): Permanently discontinue if seizure occurs 2, 1
• Severe cutaneous adverse reactions including Stevens-Johnson syndrome: Interrupt for suspected cases, permanently discontinue if confirmed 1
• Interstitial lung disease/pneumonitis: Withhold for suspected cases, permanently discontinue for severe ILD or if no other causes identified 1

Common Pitfall to Avoid

The most critical error would be discontinuing leuprolide when starting apalutamide. Both medications must be continued together—leuprolide maintains castrate testosterone levels while apalutamide blocks androgen receptor signaling 1. Stopping leuprolide would allow testosterone levels to rise, potentially accelerating cancer progression despite apalutamide therapy.