On March 28, the U.S. Food and Drug Administration (FDA) expanded the indication for lutetium Lu-177 vipivotide tetraxetan (Pluvicto) to include adults with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitor therapy and are considered appropriate to delay taxane-based chemotherapy.
Patients with previously treated mCRPC should be selected for Lu-177 vipivotide tetraxetan using gallium Ga-68 gozetotide (Locametz), a radioactive diagnostic agent for positron-emission tomography (PET) of PSMA-positive lesions, or another approved PSMA PET product based on PSMA expression in tumors.
PSMAfore
Efficacy was evaluated in PSMAfore (ClinicalTrials.gov identifier NCT04689828), a randomized, multicenter, open-label trial which enrolled 468 patients with PSMA-positive mCRPC and disease progression on one androgen receptor pathway inhibitor, who the investigator considered appropriate for delay of taxane-based chemotherapy. Patients were randomly assigned 1:1 to receive Lu-177 vipivotide tetraxetan (7.4 GBq [200 mCi] every 6 weeks for six doses) or a change in androgen receptor pathway inhibitor therapy. Patients who progressed on the androgen receptor pathway inhibitor arm were allowed to cross over to receive the experimental therapy.
The major efficacy outcome was radiographic progression–free survival by blinded independent central review; overall survival was an additional efficacy outcome. Median radiographic progression–free survival was 9.3 months (95% confidence interval [CI] = 7 months to not estimable) in the Lu-177 vipivotide tetraxetan arm and 5.6 months (95% CI = 4–6 months) in the androgen receptor pathway inhibitor arm (hazard ratio [HR] = 0.41, 95% CI = 0.29–0.56, P < .0001). Median overall survival was 24.5 months (95% CI = 19.5–28.9 months) and 23.1 months (95% CI = 19.6–25.5 months) in the respective arms (HR = 0.9, 95% C = 0.72–1.14, P = not statistically significant). Sixty percent (n = 141) of patients who were randomly assigned to receive a change in androgen receptor pathway inhibitor crossed over to receive Lu-177 vipivotide tetraxetan after disease progression.
Adverse reactions were consistent with prior experience with Lu-177 vipivotide tetraxetan. Treatment with the radioligand may result in risk from radiation exposure, myelosuppression, and renal toxicity.
The recommended Lu-177 vipivotide tetraxetan dose is 7.4 GBq (200 mCi) intravenously every 6 weeks for six doses, or until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
