Lutetium-177–PSMA-617 Radionuclide Treatment for Previously Treated Metastatic Castration-Resistant Prostate Cancer
In an Australian investigator-initiated single-center phase II study reported in The Lancet Oncology, Hofman et al found that treatment with a radiolabeled small molecule that binds to prostate-specific membrane antigen (PSMA), lutetium-177 (177Lu)–PSMA-617, produced a high response rate and improved pain symptoms in men with previously treated metastatic castration-resistant prostate cancer.
Study Details
In the study, 30 evaluable patients with high PSMA expression enrolled at the Peter MacCallum Cancer Centre between August 2015 and December 2016 received up to 4 cycles of 177Lu–PSMA-617 at 6 weekly intervals. The mean radioactivity administered was 7.5 GBq per cycle. Of the 30 patients, 26 (87%) had received at least 1 line of previous chemotherapy (80% docetaxel and 47% cabazitaxel [Jevtana]), and 25 (83%) had received abiraterone acetate (Yonsa, Zytiga), enzalutamide (Xtandi), or both.
The primary endpoints were PSA response (defined as ≥ 50% decline from baseline) and toxicity. Additional endpoints included quality of life assessed by the EORTC-Q30 and Brief Pain Inventory-Short Form, measured up to 3 months posttreatment.
Responses and Toxicities
Overall, PSA response was observed in 17 patients (57%). Objective response in nodal or visceral disease was observed in 14 (82%) of 17 patients with measurable disease. Clinically meaningful improvements in pain severity and interference scores vs baseline were observed at all time points in the study. An improvement of ≥ 10 points in global health score was observed in 11 patients (37%) by the second treatment cycle.
The most common treatment-related adverse events of any grade were grade 1 dry mouth (87%), grade 1 or 2 transient nausea (50%), and grade 1 or 2 fatigue (50%); grade 3 or 4 thrombocytopenia occurred in 13%. No treatment-related deaths were reported.
The investigators concluded, “Our findings show that radionuclide treatment with177Lu–PSMA-617 has high response rates, low toxic effects, and reduction of pain in men with metastatic castration-resistant prostate cancer who have progressed after conventional treatments. This evidence supports the need for randomised controlled trials to further assess efficacy compared with current standards of care.”
The investigators reported that there was no funding for the study.
Michael Hofman, MBBS, of the Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, is the corresponding author for The Lancet Oncology article.
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