The FDA has broadened the indication for Pluvicto to include metastatic castration-resistant prostate cancer

On March 28, 2025, the Food and Drug Administration expanded the use of lutetium Lu 177 vipivotide tetraxetan (Pluvicto, Novartis Pharmaceuticals Corporation) to include adults with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have received androgen receptor pathway inhibitor (ARPI) treatment and can wait before starting taxane-based chemotherapy.

Patients who have already received treatment for mCRPC should be identified for Pluvicto using Locametz (which contains gallium Ga 68 gozetotide) or another approved PSMA positron emission tomography (PET) product, depending on the PSMA levels in their tumors.

Effectiveness and Safety

The effectiveness was evaluated in the PSMAfore trial (NCT04689828), a study where 468 patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had not improved after one androgen receptor pathway inhibitor (ARPI) and were considered by the doctor to delay taxane-based chemotherapy participated.

Patients were randomly divided (1:1) to either receive lutetium Lu 177 vipivotide tetraxetan (7.4 GBq [200 mCi] every 6 weeks for 6 doses) or a different type of androgen receptor pathway inhibition (ARPI). Those who experienced disease progression while on the ARPI treatment could switch to the experimental treatment. Those who showed disease progression while on the ARPI treatment could switch to the experimental treatment. Patients who experienced progression on the ARPI arm were permitted to transition to the experimental treatment.

The primary effectiveness endpoint was radiographic progression-free survival (rPFS) assessed by blinded independent central review. Overall survival (OS) constituted an additional effectiveness endpoint. The median radiographic progression-free survival (rPFS) was 9.3 months (95% confidence interval [CI]: 7, not estimable) for the lutetium Lu 177 vipivotide tetraxetan group and 5.6 months (95% CI: 4, 6) for the ARPI group, with a hazard ratio (HR) of 0.41 (95% CI: 0.29, 0.56); p-value <0.0001.

The median overall survival (OS) was 24.5 months (95% CI: 19.5, 28.9) and 23.1 months (95% CI: 19.6, 25.5) in the respective groups (HR 0.91 [95% CI: 0.72, 1.14]; the p-value was not statistically significant). Sixty percent (n=141) of the patients who were randomly chosen to switch to ARPI later started receiving lutetium Lu 177 vipivotide tetraxetan after their disease got worse.

Adverse effects were consistent with previous experiences involving lutetium Lu 177 vipivotide tetraxetan. Using lutetium Lu 177 vipivotide tetraxetan for treatment may carry risks of radiation exposure, reduced bone marrow function, and kidney damage.

The recommended dose of lutetium Lu 177 vipivotide tetraxetan is 7.4 GBq (200 mCi) given through an IV every 6 weeks for a total of 6 treatments, or until the disease gets worse or side effects become too severe.