LuPSMA trial: single-arm phase 2 study of 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer
In an early single-hospital study, most men with advanced prostate cancer who had run out of standard treatments saw their PSA fall by at least half after being treated with the radioactive drug lutetium-177 PSMA-617, with mild side effects.
Overview
Conducted at Peter MacCallum Cancer Centre, Melbourne, this single-arm, single-centre phase 2 trial treated men with metastatic castration-resistant prostate cancer who had progressed after taxane chemotherapy and second-generation anti-androgens. Screening 68Ga-PSMA-11 and FDG PET/CT confirmed high PSMA expression before treatment; eligible men received up to four cycles of 177Lu-PSMA-617 (mean 7.5 GBq per cycle) six weeks apart. Endpoints were PSA response (≥50% decline), imaging response, toxicity and quality of life.
Of 43 men screened, 30 were treated. Seventeen of 30 (57%, 95% CI 37-75) had a PSA decline of 50% or more. Objective response in nodal or visceral disease was seen in 14 of 17 (82%) evaluable patients. Toxicity was mostly low grade (dry mouth in 87%, transient nausea and fatigue in 50%), though grade 3-4 thrombocytopenia occurred in 13%. Clinically meaningful pain and global-health-score improvements were recorded from the second cycle onward in over a third of patients.
This was one of the pivotal early single-arm studies (alongside German centres' compassionate-use experience) that generated the response-rate and toxicity signal used to justify the subsequent randomised trials TheraP and VISION, and it is one of the most-cited early efficacy reports for PSMA radioligand therapy.
- 17 of 30 patients (57%, 95% CI 37-75) achieved a PSA decline of 50% or more.
- Objective response in nodal or visceral disease in 14 of 17 (82%) evaluable patients.
- Grade 1 dry mouth in 87%, grade 1-2 nausea and fatigue each in 50%; grade 3-4 thrombocytopenia in 13% (4 of 30).
- 37% of patients had a 10-point or greater improvement in global health score by the second treatment cycle; no treatment-related deaths.
In a small early trial, most heavily pre-treated men with advanced prostate cancer responded to the PSMA-targeted radioactive drug, with manageable side effects, supporting the case for testing it in larger randomised trials.
- Single-arm, single-centre design with no comparator - response rates cannot be attributed to the drug alone with the same confidence as a randomised trial.
- Small sample size (30 treated patients) limits precision of toxicity estimates, particularly for rarer serious events.
- Patients were required to have high PSMA expression on screening PET, so results do not apply to PSMA-low disease.
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