When initiating Lutetium-177 PSMA therapy, should Abiraterone be stopped and restarted after completing therapy?

Management of Abiraterone During Lutetium-177 PSMA Therapy

Continue abiraterone (or other androgen pathway inhibitors) during and after Lutetium-177 PSMA-617 therapy without interruption. 1

Rationale for Continuing Abiraterone

The pivotal VISION trial, which established Lu-177-PSMA-617 as standard of care, specifically designed the control arm to receive "protocol-permitted standard of care" that explicitly included continuation of androgen pathway inhibitors like abiraterone and enzalutamide. 1 The trial demonstrated:

• Overall survival improvement: 15.3 vs 11.3 months (HR 0.62,95% CI 0.52-0.74, P<0.001) 1
• Progression-free survival improvement: 8.7 vs 3.4 months (HR 0.40,99.2% CI 0.29-0.57, P<0.001) 1

These benefits were achieved while patients continued their androgen pathway inhibitors, not by stopping them. 1

Treatment Algorithm

Before Initiating Lu-177 PSMA-617:

• Confirm eligibility: Prior treatment with at least one androgen pathway inhibitor (abiraterone or enzalutamide) AND at least one taxane (docetaxel) 1, 2, 3
• Obtain PSMA PET imaging: Must demonstrate PSMA-positive disease without PSMA non-expressing lesions 1, 2, 3
• Continue current abiraterone: Do not discontinue 1

During Lu-177 PSMA-617 Treatment:

• Maintain abiraterone with prednisone: Standard dosing of 1,000 mg daily (or 500 mg with low-fat breakfast) plus prednisone 5 mg twice daily 1
• Administer Lu-177 PSMA-617: 7.4 GBq (200 mCi) every 6 weeks for 4-6 cycles 1, 2, 3
• Monitor concurrently: Check blood counts, liver function, potassium, phosphate, and blood pressure monthly during abiraterone therapy 1

After Completing Lu-177 PSMA-617:

• Continue abiraterone indefinitely: Maintain until disease progression or unacceptable toxicity 1
• Do not stop based on Lu-177 completion alone: The combination provides ongoing androgen suppression while Lu-177 effects persist 1

Critical Evidence Supporting Continuation

The ESMO guidelines explicitly recommend Lu-177-PSMA-617 "in men with cancer expressing PSMA on PET-PSMA and without PSMA non-expressing lesions" who have received "a novel androgen receptor axis inhibitor (abiraterone, apalutamide, darolutamide or enzalutamide) and docetaxel." 1 This recommendation (ESMO-MCBS v1.1 score: 4, the highest benefit score) assumes continuation of hormonal therapy as part of best standard of care. 1

The AUA/SUO guidelines similarly provide a Strong Recommendation (Evidence Level: Grade B) for Lu-177-PSMA-617 in patients with "progressive mCRPC having previously received docetaxel and androgen pathway inhibitor," without any instruction to discontinue the androgen pathway inhibitor. 1

Common Pitfalls to Avoid

• Do not stop abiraterone when starting Lu-177: This was not done in the VISION trial and would remove a proven survival benefit 1
• Do not restart abiraterone after Lu-177 if it was working: It should never have been stopped in the first place 1
• Do not switch abiraterone formulations during treatment: Switching from standard to fine-particle formulation (or vice versa) on disease progression is not recommended 1
• Do not discontinue steroids with abiraterone: Continue prednisone or methylprednisolone to prevent mineralocorticoid excess (hypertension, hypokalemia, edema) 1

Monitoring During Combined Therapy

• Monthly assessments initially: Liver function, potassium, phosphate, blood pressure for abiraterone monitoring 1
• Before each Lu-177 cycle: Complete blood count, renal and hepatic function 2, 3
• PSA measurements: Before each Lu-177 cycle to assess response 2, 3
• Imaging: PSMA PET at baseline and after completion of Lu-177 therapy or at PSA progression 1, 4

Additional Considerations

Bone protection is mandatory: Start denosumab or zoledronic acid before Lu-177 therapy to reduce fracture risk, as demonstrated in the PEACE III trial (fracture rates 2.8% with bone protection vs 45.9% without). 3

Quality of life is preserved: The VISION trial showed no difference in quality of life between Lu-177 plus standard of care versus standard of care alone, despite higher grade 3-4 adverse events (52.7% vs 38%). 1 This supports the safety of continuing abiraterone during Lu-177 therapy.