FDA broadens Pluvicto's use for metastatic castration-resistant prostate cancer

On March 28, 2025, the Food and Drug Administration (FDA) broadened the use of lutetium Lu 177 vipivotide tetraxetan, commercially known as Pluvicto by Novartis Pharmaceuticals Corporation. This expanded indication now includes adults suffering from prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with androgen receptor pathway inhibitor (ARPI) therapy and are considered candidates for postponement of taxane-based chemotherapy.

To determine eligibility for Pluvicto, patients with previously treated mCRPC should be assessed using Locametz, which contains the active ingredient gallium Ga 68 gozetotide, or any other approved PSMA positron emission tomography (PET) product, based on the expression of PSMA in tumors. Comprehensive prescribing details for Pluvicto will be accessible on the Drugs@FDA website.

The effectiveness of this treatment was assessed in the PSMAfore clinical trial (NCT04689828), which was a randomized, multicenter, and open-label study. The trial included 468 participants with PSMA-positive mCRPC who had shown disease progression after one ARPI treatment, and who were considered suitable for a delay in taxane-based chemotherapy. Participants were randomly assigned in equal numbers to receive either lutetium Lu 177 vipivotide tetraxetan, administered at 7.4 GBq (200 mCi) every six weeks for up to six doses, or a switch in ARPI therapy. Patients whose cancer progressed on the ARPI treatment arm were given the opportunity to switch to the experimental therapy.

The primary measure of effectiveness was radiographic progression-free survival (rPFS), appraised by an independent central review. Overall survival (OS) served as an additional measure of effectiveness. The trial demonstrated a median rPFS of 9.3 months in those receiving lutetium Lu 177 vipivotide tetraxetan, compared to 5.6 months for those on the ARPI regimen, with a hazard ratio of 0.41 and a highly significant p-value of less than 0.0001. Median overall survival rates were slightly closer, with 24.5 months for the lutetium Lu 177 vipivotide tetraxetan group and 23.1 months for the ARPI group, with a hazard ratio of 0.91. However, these results were not statistically significant. Notably, 60% of patients assigned to the ARPI arm transitioned to the experimental treatment with lutetium Lu 177 vipivotide tetraxetan after their disease progressed.

Adverse reactions observed with lutetium Lu 177 vipivotide tetraxetan were consistent with those from prior experiences. Potential risks associated with this treatment include radiation exposure, myelosuppression, and renal toxicity. The advised dosage for lutetium Lu 177 vipivotide tetraxetan is 7.4 GBq (200 mCi) administered intravenously every six weeks, extending for up to six doses or until either disease progression occurs or unacceptable toxicity levels are reached.

The FDA's review process for this expanded indication utilized the Assessment Aid, a voluntary submission by the applicant designed to streamline the FDA's evaluation process. Healthcare professionals are encouraged to report any serious adverse events linked to the use of this or any medical product to the FDA's MedWatch Reporting System.