Dr Tagawa on the Safety Profile of Lutetium Lu 177 Vipivotide Tetraxetan Plus ARPI and ADT in PSMA+ mHSPC

“This was the third phase 3 [study] with [lutetium Lu 177 vipivotide tetraxetan] so there was not much in the way of surprise [in terms of safety].”

Scott T. Tagawa, MD, MS, FACP, FASCO, a professor of medicine and urology at Weill Cornell Medicine and an attending physician at NewYork-Presbyterian – Weill Cornell Medical Center, discussed safety data from the phase 3 PSMAddition trial (NCT04720157) of an androgen receptor pathway inhibitor (ARPI) and androgen deprivation therapy (ADT) with or without evaluated lutetium Lu 177 vipivotide tetraxetan (Pluvicto) for the treatment of patients with prostate specific-membrane antigen (PSMA)–positive metastatic hormone-sensitive prostate cancer (mHSPC), which were presented during the 2025 ESMO Congress.

Tagawa began by noting that this is the third phase 3 study of lutetium Lu 177 vipivotide tetraxetan and that the safety profile was consistent with what was observed in the previous studies. The most common any-grade adverse effects (AEs) among patients who received lutetium Lu 177 vipivotide in combination with an ARPI and ADT (n = 564) included dry mouth (45.7%), fatigue (34.8%), and nausea (34.2%). These effects were correlated with sites of normal PSMA expression, such as the salivary glands, lacrimal glands, and the small intestine, Tagawa explained.

Notably, hormonal AEs were more common in the control arm (n = 565), Tagawa said. These included any-grade hot flush (36.3%) and hypertension (16.8%), he added. Instances of high-grade cytopenias in the investigational arm were rare, he concluded.

Any-grade AEs related to any study treatment occurred in the investigational and control arms at respective rates of 89.4% and 69.7%. Patients in both arms also experienced AEs leading to death (2.7% vs 2.5%), treatment discontinuation (16.1% vs 9.0%), and serious AEs (31.9% vs 28.7%). Importantly, no AEs leading to death were attributed to study treatment in either arm.