Continuing ADT and Apalutamide During LU-177 Therapy for Prostate Cancer
Patients with prostate cancer should continue androgen deprivation therapy (ADT) and apalutamide during Lutetium-177 (LU-177) infusions to maximize survival benefits through complementary mechanisms of action targeting different aspects of tumor growth and progression. 1
Rationale for Continuing ADT
Mechanism and Guidelines
- ADT remains the backbone therapy for all stages of advanced prostate cancer, including during other treatments
- Clinical guidelines explicitly state that patients with castration-resistant prostate cancer (CRPC) should continue with life-long ADT 1
- Continuing ADT maintains castrate levels of testosterone (<50 ng/dL), which is essential even when cancer becomes castration-resistant 1
- Discontinuing ADT can lead to testosterone recovery and accelerated disease progression
Rationale for Continuing Apalutamide
Mechanism of Action
- Apalutamide is an androgen receptor (AR) inhibitor that works differently from traditional ADT 2
- It binds directly to the ligand-binding domain of the AR
- Inhibits AR nuclear translocation, DNA binding, and AR-mediated transcription
- Decreases tumor cell proliferation and increases apoptosis 2
Clinical Evidence
- The SPARTAN trial demonstrated that apalutamide plus ADT significantly improved metastasis-free survival (40.5 vs 16.2 months) compared to ADT alone in non-metastatic CRPC 1
- The TITAN trial showed apalutamide plus ADT improved radiographic progression-free survival and overall survival in metastatic castration-sensitive prostate cancer 3
- Guidelines recommend apalutamide with continued ADT for non-metastatic CRPC at high risk for developing metastatic disease (Standard; Evidence Level Grade A) 1
Synergistic Effects with LU-177 Therapy
Complementary Mechanisms
- LU-177 PSMA-617 radioligand therapy targets PSMA-expressing tumor cells directly through radiation
- ADT and apalutamide target the androgen receptor pathway
- Recent evidence suggests that combining LU-177 PSMA-617 with androgen receptor pathway inhibitors (ARPIs) like apalutamide significantly improves progression-free survival (11 vs 5.6 months) compared to LU-177 alone 4
Clinical Benefits of Combination
- Combination therapy with LU-177 and ARPIs showed a trend toward improved overall survival (20.3 vs 15.9 months) 4
- The combination approach targets both hormone-dependent and hormone-independent cancer cells
- Continuing ADT and apalutamide may enhance the efficacy of LU-177 by preventing tumor regrowth between LU-177 cycles
Practical Considerations
Monitoring During Therapy
- Regular PSA monitoring to assess treatment response
- Testosterone levels should be maintained at castrate levels (<50 ng/dL)
- Monitor for potential side effects specific to the combination therapy
Potential Side Effects to Monitor
- Rash (more common with apalutamide - 23.8% vs 5.5% with placebo) 1
- Fatigue, hypertension, and falls
- Thyroid function changes (hypothyroidism occurred in 8.1% with apalutamide vs 2.0% with placebo) 1
- Bone marrow suppression (primarily from LU-177)
Conclusion
Continuing ADT and apalutamide during LU-177 therapy represents an evidence-based approach that targets prostate cancer through multiple mechanisms, maximizing treatment efficacy and improving survival outcomes. The combination therapy provides complementary effects that can lead to better disease control than any single treatment alone.