FDA Expands Lutetium Lu 177 Vipivotide Tetraxetan to mHSPC, Nearly Doubling Eligible Population

The FDA has approved lutetium Lu 177 vipivotide tetraxetan (Pluvicto; Novartis) in combination with an androgen receptor pathway inhibitor (ARPI) for adults with prostate-specific membrane antigen (PSMA)-positive metastatic androgen pathway modulation-naïve or -sensitive prostate cancer, previously referred to as metastatic hormone-sensitive prostate cancer (mHSPC).

The expanded indication moves PSMA-targeted radioligand therapy earlier in the disease course and nearly doubles the population eligible to receive lutetium Lu 177 vipivotide tetraxetan.¹

Earlier Precision Treatment Across Metastatic Disease

Lutetium Lu 177 vipivotide tetraxetan was previously indicated for PSMA-positive metastatic androgen pathway modulation-resistant prostate cancer, historically called metastatic castration-resistant prostate cancer, following ARPI therapy in patients who were appropriate to delay taxane chemotherapy or had previously received a taxane. The new indication makes the agent available across the PSMA-positive metastatic prostate cancer continuum.²

This expansion is clinically significant because mHSPC remains incurable despite advances in treatment intensification. Approximately half of patients progress to castration-resistant disease within 20 months, and nearly one-third do not achieve an undetectable prostate-specific antigen level with an ARPI plus androgen deprivation therapy (ADT).³ Earlier incorporation of a biomarker-directed treatment may therefore provide another strategy for delaying progression.

PSMAddition Demonstrates Improved Disease Control

Approval was supported by PSMAddition (NCT04720157), a phase 3, randomized, multicenter, open-label trial enrolling patients with PSMA-positive disease. Participants received lutetium Lu 177 vipivotide tetraxetan plus an investigator-selected ARPI or an ARPI alone. All patients also received a gonadotropin-releasing hormone agonist or antagonist or had undergone bilateral orchiectomy.¹

At the primary analysis, the addition of lutetium Lu 177 vipivotide tetraxetan reduced the risk of radiographic progression or death by 28% compared with standard therapy alone (HR, 0.72; 95% CI, 0.58-0.90; P = .002). Median radiographic progression-free survival was not reached in either treatment group.¹

A subsequent analysis showed a 33% reduction in the risk of progression or death (HR, 0.67; 95% CI, 0.55-0.82). Overall survival data remained immature but demonstrated a favorable trend with the combination (HR, 0.80; 95% CI, 0.63-1.01).³

Pharmacists Support Safe Radioligand Therapy Delivery

Lutetium Lu 177 vipivotide tetraxetan combines a PSMA-targeting ligand with the radioactive isotope lutetium-177, delivering radiation to PSMA-expressing tumor cells and surrounding cells. Patients must be selected using gallium-68 gozetotide (Locametz; Novartis) or another FDA-approved PSMA positron emission tomography product. The recommended dose is 7.4 GBq, or 200 mCi, intravenously every 6 weeks for 6 doses or until progression or unacceptable toxicity.^1,2

In PSMAddition, grade 3 or higher adverse events occurred in 50.7% of patients receiving the radioligand combination and 43.0% receiving standard therapy. Common adverse events (AEs) included fatigue, dry mouth, nausea, hot flush, and anemia.³ The prescribing information includes warnings for radiation exposure, myelosuppression, renal toxicity, embryo-fetal toxicity, and infertility.²

Oncology pharmacists will be central to coordinating laboratory monitoring, hydration, AE management, radiation-safety counseling, and communication among oncology, nuclear medicine, and infusion teams. Continued investigation, including the phase 3 PSMA-DC trial (NCT05939414) in PSMA-positive oligometastatic prostate cancer, may move this approach into even earlier disease settings.⁴

REFERENCES

1. FDA approves lutetium Lu 177 vipivotide tetraxetan with androgen receptor pathway inhibitor therapy for metastatic androgen pathway modulation-naïve or -sensitive prostate cancer. FDA. Published July 31, 2026. Accessed August 3, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-vipivotide-tetraxetan-androgen-receptor-pathway-inhibitor-therapy

2. Pluvicto (lutetium Lu 177 vipivotide tetraxetan) prescribing information. Novartis Pharmaceuticals Corporation. Revised July 2026. Accessed August 3, 2026. https://www.novartis.com/us-en/sites/novartis_us/files/pluvicto.pdf

3. FDA approves Pluvicto for PSMA+ metastatic hormone-sensitive prostate cancer, advancing potential new standard of care across metastatic disease. Novartis. Published July 31, 2026. Accessed August 3, 2026. https://www.novartis.com/news/media-releases/fda-approves-pluvicto-psma-metastatic-hormone-sensitive-prostate-cancer-mhspc-advancing-potential-new-standard-care-across-metastatic-disease

4. An open-label study comparing lutetium (177Lu) vipivotide tetraxetan versus observation in PSMA-positive OMPC. Novartis Clinical Trials. NCT05939414. Published June 10, 2026. Accessed August 3, 2026. https://www.novartis.com/clinicaltrials/study/nct05939414