FDA Approves Pluvicto for PSMA+ mAPMN/S Prostate Cancer

The U.S. Food and Drug Administration (FDA) has announced the approval of lutetium Lu 177 vipivotide tetraxetan (Pluvicto, Novartis Pharmaceuticals Corporation) for use in combination with androgen receptor pathway inhibitor (ARPI) therapy. This new indication specifically targets adults with prostate-specific membrane antigen (PSMA)-positive metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer.

This patient population was previously characterized as having metastatic hormone-sensitive prostate cancer (mHSPC). This approval marks a significant expansion for the radioligand therapy, moving it earlier in the treatment continuum for patients with metastatic disease.

Evidence from the PSMAddition Trial

The FDA's decision was primarily supported by findings from the PSMAddition trial (NCT04720157), a randomized, multicenter, open-label study. The trial enrolled patients with PSMA-positive mAPMN/S prostate cancer, who were randomized in a 1:1 ratio to receive either the Pluvicto combination or an ARPI alone.

Patients in the experimental arm received lutetium Lu 177 vipivotide tetraxetan at a dose of 7.4 GBq (200 mCi) every six weeks for up to six doses, alongside an investigator’s choice of ARPI. The permitted ARPIs in the trial included abiraterone, apalutamide, enzalutamide, or darolutamide. All participants also received concurrent gonadotropin-releasing hormone (GnRH) therapy or had previously undergone a bilateral orchiectomy.

The primary efficacy endpoint was radiographic progression-free survival (rPFS), as determined by a blinded independent central review. The results demonstrated a statistically significant improvement for those receiving the combination therapy. The hazard ratio for rPFS was 0.72 (95% CI: 0.58, 0.90; p-value 0.002). The median rPFS had not yet been reached in either arm at the time of the analysis. While overall survival (OS) was also measured, the data were considered immature during this review period.

Nursing Considerations: Selection and Administration

For oncology nurses, understanding the patient selection process is paramount. Patients must be identified as PSMA-positive using an approved diagnostic tool. The FDA specifies that Locametz (gallium Ga 68 gozetotide) or another approved PSMA positron emission tomography (PET) imaging product should be used to confirm PSMA expression in tumors prior to initiating treatment.

The administration schedule requires careful coordination:

• Dose: 7.4 GBq (200 mCi).
• Frequency: Every six weeks.
• Duration: Up to six total doses, or until disease progression or unacceptable toxicity.

Safety Profile and Monitoring

The adverse reactions observed in the PSMAddition trial were consistent with the established safety profile of lutetium Lu 177 vipivotide tetraxetan. However, oncology nurses should be vigilant regarding several specific warnings and precautions included in the prescribing information:

• Radiation Exposure: Because Pluvicto is a radiopharmaceutical, nurses must ensure that safety protocols are followed to minimize radiation exposure to the patient, healthcare providers, and the patient's household members.
• Myelosuppression: Patients may experience significant cytopenias. Regular monitoring of complete blood counts is essential.
• Renal Toxicity: Radioligand therapies can impact kidney function. Nurses should monitor renal labs and encourage adequate hydration.
• Embryo-Fetal Toxicity and Infertility: The treatment carries risks for reproductive health, necessitating clear communication with patients regarding contraception and potential long-term effects on fertility.

The FDA utilized the Assessment Aid for this review, a voluntary submission that helped streamline the process, resulting in an approval one month ahead of the scheduled goal date.

Key Takeaways for Oncology Nurses

• Expanded Indication: Pluvicto is now approved for PSMA-positive metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer (formerly mHSPC) when used with an ARPI.
• Proven Efficacy: The combination improves rPFS (HR 0.72) compared to ARPI therapy alone.
• Diagnostic Requirement: PSMA positivity must be confirmed via PET imaging (e.g., Locametz) before treatment begins.
• Specific Dosing Schedule: Treatment consists of six doses administered at six-week intervals.
• Critical Safety Oversight: Nurses must manage and educate patients on risks including radiation safety, myelosuppression, and renal toxicity.
• Reporting: Healthcare professionals are encouraged to report any serious adverse events to the FDA's MedWatch Reporting System.

Reference

1. FDA approves lutetium Lu 177 vipivotide tetraxetan with androgen receptor pathway inhibitor therapy for metastatic androgen pathway modulation-naïve or -sensitive prostate cancer. U.S. Food and Drug Administration. July 31, 2026. Accessed July 31, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-vipivotide-tetraxetan-androgen-receptor-pathway-inhibitor-therapy