PMID-29752180 – LuPSMA Phase 2 Trial Lu-177-PSMA-617 in mCRPC
Hofman MS, Violet J, Hicks RJ, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19(6):825-833.
Quick Reference
| Property | Value |
|---|---|
| PMID | 29752180 |
| DOI | 10.1016/S1470-2045(18)30198-0 |
| Year | 2018 |
| Journal | The Lancet Oncology |
| Study Type | Observational (Phase 2, single-arm) |
| Evidence Level | III |
| Sample | 30 patients with mCRPC |
| Peptide(s) Studied | Lutetium-177-PSMA-617 |
Key Findings
- PSA decline >=50% achieved in 57% (17/30) of patients (95% CI 37-75%)
- Objective response in measurable disease: 82% (14/17 evaluable patients)
- No treatment-related deaths
- Dry mouth was the most common AE (87%, all grade 1)
- Grade 3-4 thrombocytopenia in 13% (4 patients)
- 26 of 30 patients had received prior chemotherapy; 25/30 had prior abiraterone/enzalutamide
- Median overall survival was 13.5 months from first cycle
- Quality of life improved significantly from baseline
Study Design
Single-center, single-arm, Phase 2 study (NCT02683370) at Peter MacCallum Cancer Centre, Melbourne, Australia. 30 eligible patients with progressive PSMA-positive mCRPC received up to 4 cycles of 177Lu-PSMA-617 (7.5 GBq IV) at 6-week intervals. Primary endpoint: PSA response (>=50% decline). PSMA positivity confirmed by 68Ga-PSMA PET/CT with SUVmax > 20.
Limitations
- Single-arm design without comparator
- Small sample size (n=30)
- Single-center study, limiting generalizability
- Strict PSMA-positivity criteria (SUVmax > 20) selected for high-PSMA expressors
- Short follow-up period
Clinical Relevance
The LuPSMA trial was the first prospective clinical trial of 177Lu-PSMA-617, providing critical proof-of-concept data that justified the large Phase 3 VISION trial. The 57% PSA response rate and 82% objective response rate in a heavily pretreated population were remarkably high for late-line mCRPC therapy. This study established the feasibility and safety of PSMA-targeted radioligand therapy and launched a new therapeutic paradigm in prostate oncology.
Related
#research #observational #lutetium-177-PSMA-617 #evidence-level-III