A RADIOACTIVE drug that targets prostate cancer cells directly has shown early success at delaying disease progression when added to standard hormone therapy, a new study shows.
The PSMAddition trial found adding lutetium-177 PSMA-617, a radioligand therapy that seeks out and irradiates cancer cells bearing a marker called prostate-specific membrane antigen (PSMA), improves outcomes for men with metastatic prostate cancer that still responds to hormone treatment.
Lower Risk of Progression
Researchers randomised 1,144 patients with PSMA-positive metastatic hormone-sensitive prostate cancer to receive either standard hormone therapy alone or the same treatment combined with lutetium-177 PSMA-617.
The drug works by binding to PSMA, a protein found on the surface of prostate cancer cells, and delivering a localised dose of radiation while sparing much of the surrounding healthy tissue.
Results showed that patients who received the added radioligand therapy had a 28% lower risk of radiographic progression of their tumours or death compared with those on hormone therapy alone.
Median progression-free survival had not yet been reached in either group at the time of analysis, reflecting a slower-than-expected rate of disease progression across the trial overall.
The benefit of the combined radioactive and hormone therapies held steady across patient subgroups, including those with higher and lower volumes of disease at diagnosis.
Patients on the combination treatment also saw deeper reductions in prostate-specific antigen, a marker used to track disease activity and took longer to develop resistance to hormone therapy.
Mixed Signals on Survival and Quality of Life
Despite the progression-free survival benefit, overall survival data remains immature, and no statistically significant difference in survival between the two groups emerged from the trial.
Researchers noted that this picture could become harder to interpret over time because patients in the control group were allowed to cross over to the radioligand therapy once their disease progressed.
Overall, patients in both groups had broadly similar quality of life measures over the longer term, although scores dipped somewhat more in the treatment group during the first several months before evening out.
Rates of side effects were also higher among patients receiving the added therapy, with roughly half of patients (50.7%) on the added drug reporting a significant side effect compared with 43% on standard treatment alone, though researchers reported no unexpected safety concerns.
A New Chapter for Radioligand Therapy in Early Stage Cancer
The findings mark the first phase III evidence for a targeted radioligand therapy used this early in prostate cancer treatment, rather than after the disease has already become resistant to hormone therapy, where such drugs have previously been used.
Following the trial results, in July the US Food and Drug Administration’s approved the hormone and radiation combination for use in patients with this type of prostate cancer as an early treatment, which was previously only available to those with disease progression.
Researchers say longer follow-up will be needed to determine whether the progression-free survival benefit ultimately translates into longer lives and to build a fuller picture of long-term safety.
Reference
Tagawa S et al. [177Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial. Lancet. 2026.
Featured image: Tyler Olson on AdobeStock
