FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication
Regulatory approval: On March 28, 2025, the FDA expanded the indication for lutetium Lu 177 vipivotide tetraxetan (Pluvicto) to adults with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) previously treated with an androgen receptor pathway inhibitor (ARPI) and considered appropriate to delay taxane-based chemotherapy. The decision was supported by PSMAfore (NCT04689828), where Pluvicto improved radiographic progression-free survival versus a change in ARPI; overall survival was not statistically significant, with substantial crossover from the control arm.
FDA expands Pluvicto indication in PSMA-positive mCRPC (regulatory approval)
On March 28, 2025, the FDA expanded the indication for lutetium Lu 177 vipivotide tetraxetan (Pluvicto; Novartis) to include adults with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have received androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy.
For patients with previously treated mCRPC, selection for Pluvicto should be based on tumor PSMA expression using Locametz (gallium Ga 68 gozetotide) or another approved PSMA PET product.
Supporting trial: PSMAfore (NCT04689828)
PSMAfore was a randomized, multicenter, open-label trial (n=468) in PSMA-positive mCRPC with progression on one ARPI. Patients were randomized 1:1 to Pluvicto 7.4 GBq (200 mCi) every 6 weeks for 6 doses or a change in ARPI; 60% (n=141) of control patients crossed over to Pluvicto after progression.
Primary outcome (rPFS, BICR): median 9.3 months (95% CI 7, NE) vs 5.6 months (95% CI 4, 6); HR 0.41 (95% CI 0.29–0.56); p<0.0001.
OS: median 24.5 vs 23.1 months; HR 0.91 (95% CI 0.72–1.14); not statistically significant.
Adverse reactions were consistent with prior experience; risks include radiation exposure, myelosuppression, and renal toxicity. The recommended dose is 7.4 GBq IV every 6 weeks for 6 doses, or until progression/unacceptable toxicity.