PSMAddition: 177Lu-PSMA-617 Benefits mHSPC Across Disease Burdens

In an on-site interview at the 2026 ASCO Annual Meeting, Fred Saad, MD, of Montreal Cancer Institute, discusses subgroup findings from the phase 3 PSMAddition trial (NCT04720157) evaluating the addition of ¹⁷⁷Lu-PSMA-617 (Pluvicto) to androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC).

Saad explains the background of the primary PSMAddition analysis, which previously demonstrated a statistically significant improvement in radiographic progression-free survival (rPFS) with the addition of ¹⁷⁷Lu-PSMA-617, achieving a hazard ratio of 0.72 vs ADT plus ARPI alone. The subgroup analysis presented at ASCO examined whether treatment benefit differed according to disease volume and disease presentation, including patients with high- vs low-volume disease and those with de novo vs recurrent mHSPC.

According to Saad, the results were highly consistent across all evaluated subgroups, with rPFS hazard ratios ranging from 0.72 to 0.74. Improvements in additional efficacy end points, including time to PSA progression and time to metastatic castration-resistant prostate cancer, also generally mirrored the findings seen in the overall study population. Importantly, patient-reported outcomes and safety findings remained consistent regardless of disease burden, providing reassurance that lower-volume patients did not experience disproportionate toxicity from the radioligand therapy.

Saad notes that while the findings support broad applicability of ¹⁷⁷Lu-PSMA-617 in mHSPC, treatment decisions should still be individualized. He highlights the limitations of traditional high- and low-volume classifications and suggests that emerging imaging approaches, including PSMA PET, may help clinicians more precisely define disease burden and refine patient selection in the future.