Lutetium-177 PSMA-617 Delays Progression in Early-Stage Prostate Cancer

In an interview, Scott Tagawa, MD, Weill Cornell Medicine, discusses the PSMAddition trial presented at the 2025 ESMO Congress.

The phase 3 PSMAddition trial demonstrated that the radioligand therapy Lutetium-177 PSMA-617 (Pluvicto) provides a statistically significant and clinically meaningful benefit when added to standard of care (SOC) for patients with prostate-specific membrane antigen (PSMA)-positive metastatic hormone-sensitive prostate cancer (mHSPC).

This open-label, randomized study compared the combination of Lutetium-177 PSMA-617 plus SOC against SOC alone, where SOC consisted of androgen receptor pathway inhibitor (ARPI) therapy combined with androgen deprivation therapy (ADT). The patient population included patients with PSMA-positive disease, confirming the presence of the prostate-specific membrane antigen target.

The primary end point of the trial, radiographic progression-free survival (rPFS)—defined as the time until radiographic progression or death—showed a robust improvement in patients receiving the Lutetium-177 PSMA-617 combination. This finding is considered a critical step, as it suggests the drug can effectively delay the growth and spread of the cancer in an earlier stage of the disease.

In addition to the primary outcome, the trial also revealed a promising trend in overall survival (OS), a key secondary end point. The data suggest that incorporating this targeted radioligand therapy earlier could improve long-term outcomes and potentially address the formidable challenge of delaying the progression from hormone-sensitive to castration-resistant disease. Furthermore, the combination maintained a favorable safety profile.

This is the third successful phase 3 trial for Lutetium-177 PSMA-617, which is already FDA-approved for a later disease setting (metastatic castration-resistant prostate cancer). The positive results from PSMAddition reinforce confidence in its therapeutic value and position it as a potential new treatment option for mHSPC.