ESMO 2025 Adding 177Lu-PSMA-617 improves progression-free survival in metastatic hormone-sensitive prostate cancer

MedNet.nl: Adding 177Lu-PSMA-617 to androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) prolongs radiological progression-free survival (rPFS) in men with metastatic hormone-sensitive prostate cancer (mHSPC). PSMAddition is the first phase 3 study to investigate radioligand therapy in the setting of mHSPC, the researchers said.

The study included 1144 patients with mHSPC who had not yet received treatment for this condition, or had received minimal treatment. A prerequisite was that the disease was PSMA-positive, defined as at least one PSMA-positive metastasis on the 68Ga-PSMA-11 PET/CT scan. Patients were randomized to receive 177Lu-PSMA-617 plus ADT plus ARPI (n=572) or ADT plus ARPI alone (n=572). The primary endpoint was rPFS. Patients in the control arm could switch to the other group upon confirmed progression.

After a median follow-up of 23.6 months, rPFS was significantly longer in the 177Lu-PSMA-617 arm, with a 28% lower risk of progression. Median rPFS had not yet been reached in either group, but the number of events was significantly lower in the intervention group (24.3 vs 30.1%; HR=0.72). All subgroups studied benefited from the addition of 177Lu-PSMA-617. Median overall survival had also not yet been reached in either group, and there were insufficient deaths to analyze survival. However, a positive trend toward improved survival was observed (HR=0.84; p=0.125). Other endpoints, such as response (85.3 vs 80.8%) and time to PSA progression, were also improved with 177Lu-PSMA-617.

However, 177Lu-PSMA-617 did lead to more side effects. Treatment-related grade ≥3 adverse events occurred in 22.7% versus 12.2% and serious side effects in 5.5% and 2.1%.By contrast, quality of life remained comparable between the two groups.

The researchers conclude that adding 177Lu-PSMA-617 to ADT and an ARPI leads to clinically relevant benefits in patients with mHSPC.

Tagawa ST, et al. Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). ESMO 2025, abstract LBA6.

This article was originally published in Dutch on MedNet.nl