Recent European Trial Report on Pluvicto (Lutetium-177 PSMA-617)
Yes, there is a recent European trial report on Pluvicto: the AlphaBet trial, published in The Lancet Oncology in January 2025, which evaluated the combination of Lutetium-177 [177Lu]Lu-PSMA-I&T with radium-223 in patients with metastatic castration-resistant prostate cancer at the Peter MacCallum Cancer Centre in Melbourne, Australia. 1
Key Findings from the AlphaBet Trial
Trial Design and Patient Population
- This was an investigator-initiated, single-centre, single-arm, phase 1/2 trial conducted between November 2022 and November 2024 1
- 37 patients were enrolled, with 36 included in the safety analysis (median age 72.5 years) 1
- Patients had progressive metastatic castration-resistant prostate cancer with at least two visible bone metastases and PSMA-positive disease (defined by maximum standardised uptake value ≥20) 1
- All patients had previous exposure to an androgen receptor pathway inhibitor 1
Treatment Protocol and Dosing
- The recommended phase 2 dose was 55.0 kBq/kg of radium-223 combined with 7.4 GBq of 177Lu-PSMA-I&T, administered intravenously every 6 weeks for up to six cycles 1
- No dose-limiting toxicities were observed during dose escalation 1
- 11 patients (31%) completed all six cycles of both treatments 1
Efficacy Outcomes
- PSA response rate of 55% (95% CI 36-72) was achieved, defined as a reduction in PSA of at least 50% 1
- 18 patients (50%) discontinued treatment early, primarily due to unequivocal disease progression (61%) or adverse events (17%) 1
- Median follow-up was 13.3 months 1
Safety Profile
- Grade 3 or higher treatment-related adverse events occurred in only 14% of patients 1
- The most common grade 3+ events were anaemia (11%) and neutropenia (8%) 1
- Non-clinically significant grade 3 lymphopenia occurred in 28% of patients 1
- No treatment-related deaths occurred 1
Context Within European Guidelines
ESMO Guideline Positioning
- The European Society for Medical Oncology (ESMO) 2023 guidelines assign 177Lu-PSMA-617 the highest benefit score (ESMO-MCBS v1.1 score: 4) for metastatic castration-resistant prostate cancer patients who have received prior androgen receptor pathway inhibition and taxane-based chemotherapy 2
- ESMO recommends 177Lu-PSMA-617 for adult patients with progressive PSMA-positive mCRPC, based on the VISION trial showing median overall survival of 15.3 months versus 11.3 months with standard care alone (HR 0.62,95% CI 0.52-0.74) 2
Treatment Selection Criteria
- PSMA-positive disease must be confirmed on PET imaging (68Ga-PSMA-11 or equivalent) with no PSMA non-expressing lesions 3
- Patients should have received at least one androgen receptor pathway inhibitor and prior docetaxel chemotherapy 3
- Standard Lu-177-PSMA therapy consists of 4-6 cycles at 6-week intervals, with each cycle delivering 7.4 GBq (200 mCi) 4
Clinical Implications
Combination Therapy Approach
The AlphaBet trial represents an important advancement by combining α-emitting (radium-223) and β-emitting (177Lu-PSMA-I&T) radiopharmaceuticals, demonstrating that this combination is safe and feasible in patients with bone metastases 1. This approach warrants further evaluation as it may address resistance mechanisms that develop with single-agent radioligand therapy 1.
Monitoring Requirements
- Blood counts, renal, and hepatic function should be checked before each treatment cycle 3
- Regular hematologic monitoring is essential as myelosuppression can be cumulative with additional cycles 4
- The European Association of Nuclear Medicine recommends continuing therapy beyond two cycles even without significant lesion reduction, as long as progression has not occurred 4
Common Pitfall to Avoid
Do not exclude patients who have received limited docetaxel treatment, as the NCCN guidelines specifically support Lu-177-PSMA therapy in this population, with the TheraP trial demonstrating 66% PSA response rates regardless of the number of docetaxel cycles received 2, 3.