FDA

FDA expands Pluvicto’s indication for metastatic castration-resistant prostate cancer

April 3, 2025

FDA expanded the indication for Pluvicto (lutetium Lu 177 vipivotide tetraxetan) to include adults with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who’ve been treated with androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy.

Patients with previously treated mCRPC should be selected for Pluvicto using Locametz (active ingredient gallium Ga 68 gozetotide) or another approved PSMA positron emission tomography (PET) product based on PSMA expression in tumors.

Efficacy

Efficacy was evaluated in the phase 3, randomized, multicenter, open-label PSMAfore trial (NCT04689828) that enrolled 468 patients with PSMA-positive mCRPC and progression on one ARPI, whom the investigator considered appropriate for delay of taxane-based chemotherapy. Patients were randomized (1:1) to receive lutetium Lu 177 vipivotide tetraxetan (7.4 GBq [200 mCi] q6wks for 6 doses) or a change in ARPI. Patients who progressed on the ARPI arm were allowed to crossover to the experimental therapy.

The major efficacy outcome was radiographic progression-free survival (rPFS) by blinded independent central review. Overall survival (OS) was an additional efficacy outcome. Median rPFS was 9.3 months (95% confidence interval [CI], 7, not estimable) in the lutetium Lu 177 vipivotide tetraxetan arm and 5.6 months (95% CI, 4-6) in the ARPI arm (hazard ratio [HR], 0.41; 95% CI, 0.29-0.56; p-value <0.0001). Median OS was 24.5 months (95% CI, 19.5-28.9) and 23.1 months (95% CI, 19.6-25.5) in the respective arms (HR, 0.91; 95% CI, 0.72-1.14]; p-value was not statistically significant). Sixty percent (n = 141) of patients who were randomized to receive a change in ARPI crossed over to receive lutetium Lu 177 vipivotide tetraxetan after progression.

Safety

Adverse reactions were consistent with prior experience with lutetium Lu 177 vipivotide tetraxetan. Treatment with lutetium Lu 177 vipivotide tetraxetan may result in risk from radiation exposure, myelosuppression, and renal toxicity.

Recommended dose

The recommended dosage of lutetium Lu 177 vipivotide tetraxetan is 7.4 GBq (200 mCi) q6wks for 6 doses, or until disease progression or unacceptable toxicity.

Sources:

FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) [package insert]. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215833s021s024lbl.pdf Revised March 2025. Accessed April 1, 2025.