Can Pluvicto Provide Durable Remission in Metastatic Castration-Resistant Prostate Cancer?
Pluvicto (177Lu-PSMA-617) does not provide durable remission in metastatic castration-resistant prostate cancer, but it does extend survival and delay progression in heavily pre-treated patients. The evidence consistently shows that while responses occur, they are typically short-lived with disease progression occurring after a median of 6-9 months 1.
Survival Benefits Without Durable Remission
The FDA approval was based on the VISION trial, which demonstrated a median overall survival of 15.3 months with Pluvicto plus best standard of care versus 11.3 months with best standard of care alone (HR 0.62, P<0.001) 2. The ESMO guidelines assign this the highest benefit score (ESMO-MCBS v1.1 score: 4) 3, 4. However, this represents a survival extension rather than durable remission—the median radiographic progression-free survival was only 8.7 months versus 3.4 months in controls 3.
Pattern of Response and Relapse
- Initial responses are common but temporary: PSA response rates of 66% have been reported in the TheraP trial 4, but these biochemical responses do not translate to long-term disease control
- Median time to progression is 6-9 months: After achieving partial response or stable disease, patients ultimately show disease progression within this timeframe 1
- Rechallenge therapy is possible: When disease progresses after initial Pluvicto treatment, rechallenge therapy appears safe and can provide additional benefit, though this further confirms the lack of durable remission from initial treatment 1
Treatment Protocol and Limitations
The standard FDA-approved regimen is 7.4 GBq (200 mCi) intravenously every 6 weeks for up to 6 doses 2. The EANM recommends 4-6 cycles at 6-week intervals 4. Dose escalation to potentially curative levels is prevented by salivary gland and kidney toxicity 5, which fundamentally limits the ability to achieve durable remissions.
Patient Selection Criteria
Pluvicto should only be used in patients who meet specific criteria 3, 4:
- PSMA-expressing tumors confirmed on PET-PSMA imaging (68Ga-PSMA-11 or equivalent)
- No PSMA non-expressing lesions (critical exclusion criterion)
- Prior treatment with at least one androgen receptor pathway inhibitor
- Prior treatment with docetaxel chemotherapy
Emerging Strategies to Improve Durability
Recent research suggests combination approaches may enhance durability:
- Combination with L19-IL2 (targeted interleukin-2) achieved complete and durable responses in all treated animals in preclinical models, whereas Pluvicto alone did not 5
- This combination works by boosting immune system activation in animals pre-treated with Pluvicto 5
- These findings warrant clinical exploration but are not yet standard of care 5
Clinical Context and Realistic Expectations
Pluvicto should be positioned as a palliative therapy that extends survival and delays progression, not as a curative treatment. The most common adverse reactions include fatigue (>20%), dry mouth (>20%), nausea (>20%), anemia (>20%), decreased appetite (>20%), and constipation (>20%) 2. Laboratory abnormalities affecting >30% of patients include decreased lymphocytes, hemoglobin, leukocytes, platelets, calcium, and sodium 2.
The ESMO guidelines recommend Pluvicto specifically for patients who have exhausted both novel androgen receptor axis inhibitors and docetaxel 3, positioning it as a late-line therapy where the goal is meaningful life extension rather than cure.