Dr Tagawa on the Rationale for Evaluating Lutetium Lu 177 Vipivotide Tetraxetan Plus ARPI and ADT in PSMA+ mHSPC

“We know, at least preclinically, that when we add hormonal therapy to a prostate cancer cell, there is upregulation of PSMA and there are also separate data [where] there may be radiosensitization.”

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 the rationale for the phase 3 PSMAddition trial (NCT04720157) of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in combination with an androgen receptor pathway inhibitor (ARPI) and androgen deprivation therapy (ADT) vs ARPI plus ADT alone in patients with prostate specific-membrane antigen (PSMA)–positive metastatic hormone-sensitive prostate cancer (mHSPC).

Tagawa began by explaining that although lutetium Lu 177 vipivotide tetraxetan received FDA approval in March 2022 for the treatment of adult patients with PSMA-positive metastatic castration-resistant prostate cancer who have previously received other anticancer therapies, such as ARPI therapy and taxane-based chemotherapy, this is not optimal. Patients with heavily-pretreated disease are more likely to have low levels of PSMA and to have greater radioresistance, he said. Moving lutetium Lu 177 vipivotide tetraxetan earlier in the therapeutic paradigm and into a disease state that more universally expresses PSMA could lead to enhanced therapeutic efficacy, he noted.

Additionally, PSMAddition is a true combination study, Tagawa said. The phase 3 VISION trial (NCT03511664), data from which supported the March 2022 approval, combined lutetium Lu 177 vipivotide tetraxetan with standard-of-care therapy, however it wasn’t always used in combination with hormonal therapy and the available hormonal therapies at the time were less active, he noted.

Findings from the preclinical study have indicated that the introduction of hormonal therapy to prostate cancer cells leads to the upregulation of PSMA and radiosensitization, which helped to inform the rationale for PSMAddition Tagawa said. Moreover, it is standard practice in drug development to move therapies forward when they show efficacy in later lines of treatment, he concluded.