177Lu-PSMA-617 Approved for PSMA+ mCRPC

The FDA has expanded the label of lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617; Pluvicto) to include indications for prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) in adults who have previously received androgen receptor pathway inhibitor (ARPI) therapy and are appropriate candidates to delay taxane-based chemotherapy, the agency has announced.¹

Eligible patients should be selected using gallium Ga 68 gozetotide or another approved PSMA-PET product used to identify PSMA expression.

Selection of patients with previously treated mCRPC who are eligible for treatment with 177Lu-PSMA-617 should be made using gallium Ga 68 gozetotide or another approved PSMA-PET product identifying PSMA expression in tumors.

Safety and Dosage

Adverse effects (AEs) were consistent with previous known experience with the drug; use of lutetium Lu 177 vipivotide tetraxetan may lead to risk from radiation exposure, myelosuppression, and renal toxicity. The FDA recommends 177Lu-PSMA-617 be administered intravenously at 7.4 GBq (200 mCi) every 6 weeks for 6 doses, or until disease progression or unacceptable toxicity.

The FDA previously approved 177Lu-PSMA-617 (Pluvicto) for mCRPC following ARPI and taxane-based chemotherapy.

Efficacy

The efficacy of 177Lu-PSMA-617 was evaluated in the randomized, multicenter, open-label trial PSMAfore (NCT04689828). The trial enrolled 468 patients who had PSMA-positive mCRPC who had experienced progression after one ARPI. Participants had to be considered eligible for the delay of taxane-based chemotherapy by investigators.

Patients were randomized 1:1 to treatment with 7.4 GBq of 177Lu-PSMA-617 every 6 weeks for 6 doses or a change in ARPI. Those who progressed in the ARPI arm were allowed to cross over to experimental treatment, which 60% (n = 141) of patients did.

Radiographic progression-free survival (rPFS) and overall survival (OS) were the primary and secondary end points, respectively. Median rPFS was 9.3 months (95% CI, 7-not estimable [NE]) for patients on the experimental drug and 5.6 months (95% CI, 4-6) for patients taking another ARPI (hazard ratio [HR], 0.41; 95% CI, 0.29-0.56; P < .0001).

Median OS for the experimental arm was 24.5 months (95% CI, 19.5-28.9) and 23.1 months (95% CI, 19.6-25.5; HR, 0.91; 95% CI, 0.72-1.14; P-value not statistically significant), respectively.

PSMAfore Trial

Phase 3 data from PSMAfore were presented at the 2023 European Society for Medical Oncology Annual Congress in Madrid, Spain, by A. Oliver Sartor, MD, a professor of medicine, urology, and radiology at Mayo Clinic in Rochester, Minnesota.²

Regarding adverse events (AEs), 77 grade 3-4 AEs were observed (33.9%) in the 177Lu-PSMA-617 group vs 100 (43.1%) in the ARPI change group. There were 46 serious AEs (20.3%) in the 177Lu-PSMA-617 group vs 65 (28.0%) in the ARPI change group. There were 8 AEs leading to dose adjustment (3.5%) in the 177Lu-PSMA-617 group vs 35 in the ARPI change group. AEs occurring in at least 10% of patients in either arm included dry mouth, asthenia, nausea, anemia, fatigue, constipation, decreased appetite, arthralgia, COVID-19, diarrhea, back pain, vomiting, peripheral edema, and weight loss.

Findings from the prespecified crossover-adjusted analysis indicated that at a median follow-up of 12.72 months, median OS was 19.25 months (95% CI, 16.95-not evaluable [NE]) in the 177Lu-PSMA-617 group and at a median follow-up of 13.08 months, median OS was 19.55 months (95% CI, 14.95-NE) in the ARPI change group.

Reference

1. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. FDA. March 28, 2025. Accessed March 28, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication
2. Sartor AO, Castellano D, Herrmann K, et al. Phase III trial of [177Lu] Lu-PSMA-617 in taxane-naive patients with metastatic castration-resistant prostate cancer (PSMAfore). Presented at: ESMO Congress 2023; October 20-24, 2023; Madrid, Spain. Abstract LBA13