FDA Approves Lutetium Lu 177 for Earlier-Stage Prostate Cancer

Lutetium Lu 177 vipivotide tetraxetan (Pluvicto; Novartis) can now be used across the full metastatic prostate cancer spectrum, after the FDA approved the radioligand therapy for patients earlier in their disease course, nearly doubling the population eligible for the targeted treatment.¹ The approval extends indications for the drug beyond its original use in treatment-resistant disease and into patients who have not yet stopped responding to hormone therapy, a shift oncologists say reflects a broader move toward earlier, more targeted intervention in prostate cancer care.²

The agency approved lutetium Lu 177 vipivotide tetraxetan in combination with an androgen receptor pathway (ARP) inhibitor for adults with prostate-specific membrane antigen (PSMA)–positive metastatic androgen pathway modulation–naive or –sensitive PC, more commonly known as metastatic hormone-sensitive PC (mHSPC).¹ To receive the medication, patients are selected based on PSMA tumor expression. This can be accomplished via Locametz (gallium Ga 68 gozetotide) or another approved PSMA PET product. The approval builds on Pluvicto’s existing indication in metastatic androgen pathway modulation-resistant PC, also called metastatic castration-resistant PC (mCRPC), which the FDA cleared in March 2025.³

How Strong Were the Clinical Trial Data?

Efficacy data came from PSMAddition (NCT04720157), a phase 3, randomized, open-label trial that assigned 1144 patients evenly to lutetium Lu 177 vipivotide tetraxetan plus an ARP inhibitor or an ARP inhibitor alone, with all patients also receiving androgen deprivation therapy or having undergone bilateral orchiectomy.¹ At the primary analysis, adding lutetium Lu 177 vipivotide tetraxetan cut the risk of radiographic progression or death by 28% (HR, 0.72; 95% CI, 0.58-0.90; P = .002), as measured by blinded independent central review.^1,2

Novartis first disclosed the 28% risk reduction, ahead of its regulatory submission, at the 2025 European Society for Medical Oncology Congress.⁴ A subsequent, updated analysis showed the benefit growing to a 33% reduction in risk (HR, 0.67; 95% CI, 0.55-0.82), along with a favorable but still-maturing overall survival trend of 20% (HR, 0.80; 95% CI, 0.63-1.01).² Median radiographic progression-free survival was not reached in either arm at the time of FDA review, and overall survival data remain immature.¹

What Does This Approval Mean for Eligible Patients and Treatment Access?

Because PSMA is expressed in more than 80% of prostate cancer cases, this biomarker-driven approach could reach a substantial share of the newly eligible population.² More than 186,000 men are diagnosed with mHSPC each year across the countries Novartis tracks, and the disease remains incurable. About a third of patients fail to reach undetectable PSA levels on ARP inhibitor-ADT doublet therapy alone, and roughly half progress to castration-resistant disease within 20 months, a window the company frames as the rationale for intensifying treatment earlier.

“The treatment landscape for mHSPC is evolving, and this approval reflects a growing recognition that earlier treatment intensification matters,” said Michael Morris, MD, prostate cancer section head, GU Oncology, Memorial Sloan Kettering Cancer Center, and a principal investigator of the study in the US, in a statement. “Having a radioligand therapy available at this stage meaningfully expands the options for physicians and represents real progress for patients.”²

Grade 3 or higher adverse events (AEs) occurred in 50.7% of patients on lutetium Lu 177 vipivotide tetraxetan plus standard of care vs 43.0% on standard of care alone, with dry mouth, fatigue, nausea, hot flush, and anemia among the most common all-grade AEs.² The FDA’s label carries warnings for radiation exposure, myelosuppression, renal toxicity, embryo-fetal toxicity, and infertility, consistent with the drug’s existing profile in mCRPC.^1,5

Novartis said it now has 5 radioligand therapy manufacturing sites operational or under construction in the US and can deliver doses to treatment sites within 5 days of order.² Because the approval requires confirming PSMA expression via PET imaging before treatment, more patients with newly diagnosed mHSPC will need this imaging step to determine eligibility.¹

The recommended dose of lutetium Lu 177 vipivotide tetraxetan is 7.4 GBq (200 mCi) every 6 weeks for 6 doses, or until disease progression or unacceptable toxicity.

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. 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. FDA approves Pluvicto for PSMA+ metastatic hormone-sensitive prostate cancer (mHSPC), advancing potential new standard of care across metastatic disease. News release. Novartis. July 31, 2026. Accessed August 3, 2026. https://www.novartis.com/us-en/news/media-releases/fda-approves-pluvicto-psma-metastatic-hormone-sensitive-prostate-cancer-mhspc-advancing-potential-new-standard-care-across-metastatic-disease
3. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. FDA. March 28, 2025. Accessed August 3, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication
4. Caffrey M. Adding radioligand therapy Pluvicto to SOC cuts risk of prostate cancer progression or death 28%, but how many doses? AJMC^®. October 20, 2025. Accessed August 3, 2026. https://www.ajmc.com/view/adding-radiogland-therapy-pluvicto-to-soc-cuts-risk-of-prostate-cancer-progression-or-death-28-but-how-many-doses-
5. Pluvicto. Prescribing information. Novartis; 2026. Accessed August 3, 2026. https://us.pluvicto.com/about-pluvicto/what-to-expect-with-pluvicto-treatment