Dr Tagawa on Factors for Lutetium Lu 177 Vipivotide Tetraxetan Use Before Docetaxel in mCRPC

“My bias is the target, PSMA; therefore, if PSMA is not there very much, then it doesn't mean that a PSMA-targeted agent can't work, but it's been shown that the PSMA PETs are a very good biomarker, specifically for PSMA small molecule, particularly with lutetium Lu 177 vipivotide tetraxetan.”

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 factors to consider when selecting between lutetium Lu 177 vipivotide tetraxetan (Pluvicto) and docetaxel for the treatment of patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) after prior treatment with an androgen receptor pathway inhibitor (ARPI).

In March 2025, the FDA expanded the indication for lutetium Lu 177 vipivotide tetraxetan to include patients with PSMA-positive mCRPC who received prior ARPI therapy who are also eligible to delay taxane-based chemotherapy. When the radioligand therapy was initially approved in March 2022, it was indicated for patients with PSMA-positive mCRPC who have previously received other anticancer therapies, such as an ARPI and taxane-based chemotherapy.

When considering lutetium Lu 177 vipivotide tetraxetan as a potential treatment, PSMA remains the key factor, Tagawa explained. If PSMA is not present, a PSMA-targeted agent could still be effective, Tagawa continued, but he noted that PSMA PET scans serve as a useful biomarker for PSMA, particularly for a PSMA small molecule like lutetium Lu 177 vipivotide tetraxetan.

Furthermore, metastases in the liver are an aspect of concern, particularly because they are a poor prognostic marker, irrespective of treatment selection, Tagawa continued. He noted that data have suggested that even when there is PSMA-positivity in select organs, such as the liver, it can be expressed at lower levels than the primary tumors; in these cases, using chemotherapy may be a better option than deferring it, he stated. Some tumors and metastases could also have homogenously high levels of PSMA, and even in cases of lower PSMA expression, metastases may still respond to treatment with radioligand therapy, he added. Nevertheless, in these scenarios, tailoring treatment based on patient characteristics matters, he asserted. For example, small molecules could be administered to patients with renal failure, although if they are receiving dialysis, focusing on the data regarding chemotherapy use is important, Tagawa contextualized. Other individual factors, such as treatment preference, matter when selecting between radiation and chemotherapy, he added.

Moreover, radioligand therapy is not as widely available as chemotherapy. However, that has changed within the past year, Tagawa emphasized. This factor could also influence when and if patients receive docetaxel with lutetium Lu 177 vipivotide tetraxetan, especially if traveling to a clinic could pose as an obstacle for patients, he concluded.