Exciting New Option for Advanced Prostate Cancer: FDA Approves Pluvicto Earlier for PSMA-Positive Metastatic Hormone-Sensitive Disease

“This approval is significant because it brings another treatment option to the hormone-sensitive metastatic prostate cancer space,” Dr. Daniel Hamstra, chair of radiation oncology at Baylor College of Medicine in Houston, tells SurvivorNet.

“Starting more than a decade ago with the addition of docetaxel chemotherapy, and more recently with androgen receptor pathway inhibitors (ARPIs) such as abiraterone, enzalutamide, and darolutamide, treatment intensification has been the dominant strategy; with some patients even receiving triplet therapy combining dual androgen ablation and chemotherapy. Radioligand therapy introduces an entirely new treatment line, one built on PSMA-PET imaging and molecular targeting rather than androgen pathway biology,” Dr. Hamstra continued.

“By allowing for this targeted radiopharmaceutical therapy to be considered earlier in the disease course, we have an opportunity to intervene before patients develop castration-resistant disease, potentially improving outcomes while maintaining quality of life,” Dr. Neha Vapiwala, professor of radiation oncology at the University of Pennsylvania in Philadelphia, tells SurvivorNet.

“This approval also reflects the growing role of radiopharmaceutical therapy as an integral component of multidisciplinary cancer care,” Dr. Vapiwala added.

WATCH: How Is Radiation Used For Metastatic Prostate Cancer?

Patients must have PSMA-positive disease confirmed on an approved PSMA PET scan and continue androgen-deprivation therapy (or have previously undergone bilateral orchiectomy). Pluvicto is added to standard hormone therapy—it is not a replacement for it.

Novartis, the manufacturer of Pluvicto, estimates the expanded indication may nearly double the eligible patient population, although eligibility depends on PSMA PET findings, disease stage, prior therapy, and clinical judgment.

Dr. Andy Chen, a radiation oncologist at Texas Oncology in Sugar Land, tells SurvivorNet that Pluvicto works by attaching a radioactive particle to the PSMA marker, allowing the drug to directly target cancer cells—particularly those in the bone.

“It’s another tool in our toolbox for treating advanced prostate cancer, in addition to chemotherapy or hormone therapy. This is another option that has been very helpful,” Dr. Chen explains.

The decision is supported by results from the Phase III PSMAddition clinical trial.

RELATED: Understanding Androgen Receptor Pathway Inhibitors For Prostate Cancer

How Pluvicto Works

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) offers a targeted treatment option for men with metastatic castration-resistant prostate cancer that is PSMA-positive.

WATCH: Radioligand Therapy: Who Is Eligible & How Does It Work?

Castration-resistant means that the cancer has continued to grow despite a reduction in testosterone levels. PSMA-positive means their tumors express the PSMA protein, which can be detected through imaging.

Pluvicto uses the PSMA molecule as a target because the protein is often found on the surface of prostate cells. While normal prostate cells have some PSMA, prostate cancer cells — especially those in advanced or aggressive stages — have a significantly higher concentration of it.

The ligand component of Pluvicto binds tightly to PSMA. Once attached, the radiolabeled component, lutetium-177, emits beta radiation over a short distance — typically a few millimeters. This radiation damages the DNA of the nearby cancer cells, causing them to die. The proximity effect of this therapy is crucial; it ensures that healthy tissues, which either don’t express PSMA or express very little of it, are exposed to far less radiation than the cancer cells.

Before receiving Pluvicto, prostate cancer patients undergo a PSMA scan to confirm that their tumor expresses the target protein.

Dr. William Kevin Kelly, Chair of Medical Oncology at Thomas Jefferson University’s Sidney Kimmel Cancer Center in Philadelphia, tells SurvivorNet, “We have to understand if your tumor takes up that protein,” Dr. Kelly notes. “If not, this drug can cause more problems than good.”

Additional eligibility criteria include appropriate bone marrow function (which produces blood cells) and healthy kidney function, as the treatment can pose risks if these conditions aren’t met.

It can be an option for these patients when they have already been treated with either hormone therapy or a combination of hormone therapy and chemotherapy.

RELATED: Why Men With Advanced Prostate Cancer Should Get the Hugely Important New PSMA PET Scan

“Pluvicto had already shown benefit in later, castration-resistant stages of disease, but this approval moves it earlier in the treatment course, giving us a precision, PSMA-targeted option at diagnosis — when about half of patients would otherwise progress to castration resistance within 20 months,” Dr. Hamstra said.

What This Means for Eligible Prostate Cancer Patients

This approval significantly expands Pluvicto’s use beyond its earlier indication in metastatic castration‑resistant prostate cancer (mCRPC).

Previously, the drug was reserved for patients who had already undergone chemotherapy. In March 2025, the FDA broadened its authorization, allowing Pluvicto to be used earlier in treatment for adults with PSMA‑positive mCRPC who had received an ARPI and were candidates to delay taxane‑based chemotherapy.

WATCH: The Promise Of Radioligand Therapy

With Pluvicto now approved across all stages of PSMA‑positive metastatic prostate cancer, the number of eligible patients has nearly doubled.

“Metastatic hormone‑sensitive prostate cancer is incurable, and about half of men progress within 20 months, highlighting the need for differentiated, precision approaches earlier in the disease journey,” Novartis said in a press release.

Novartis President Victor Bultó added, “Pluvicto is now approved across PSMA‑positive metastatic prostate cancer, nearly doubling the number of patients who may benefit from this targeted approach.”

“This new synergistic approach has the potential for substantial hope and benefit to men with prostate cancer.  It will be very interesting to see if these two combined systemic therapies can be augmented with both immunotherapy, as well as selected focal treatments, such as ablation or SBRT, to enhance the durability of response,” Dr. Jeff Jones, chair of urology research at Baylor College of Medicine in Houston, tells SurvivorNet.

RELATED: When Treatment Stops Working: Managing Metastatic Castration-Resistant Prostate Cancer

The Phase III PSMAddition Trial Behind the Approval

In the PSMAddition study, Pluvicto, combined with standard-of-care androgen receptor pathway inhibitor (blocks the testosterone from getting in the prostate cancer cells) plus androgen deprivation therapy (lowers or blocks testosterone, which fuels the growth of most prostate cancer cells), reduced the risk of disease progression or death by 28% (HR 0.72; 95% CI: 0.58–0.90) compared with standard therapy alone.

An additional analysis showed a 33% reduction in the risk of progression or death (HR 0.67; 95% CI: 0.55–0.82), along with a positive trend toward improved overall survival (HR 0.80; 95% CI: 0.63–1.01). Overall survival data are still maturing ahead of the final analysis.

Pluvicto Side Effects

Dr. Aihua Edward Yen, a medical oncologist at Baylor College of Medicine, explains that Pluvicto’s side effects depend on how the radiation behaves in the body.

“Radiation potentially can cause your blood counts to come down, so we’ll usually have to watch that very carefully. It can also go to other areas of your body where PSMA is expressed, and these would be considered off‑target effects,” he says.

Common side effects include:

• Dry mouth (xerostomia)
• Fatigue
• Stomach discomfort
• Nausea
• Vomitting
• Constipation or mild diarrhea
• Reduced appetite & Changes in taste
• Low red or white blood cell counts (anemia or leukopenia)
• Joint pain (arthralgia) or back pain

Patients require monitoring of blood counts and kidney function throughout treatment.

Questions Patients Might Ask About Pluvicto and PSMA-Targeted Therapy

• How do I know if my prostate cancer is PSMA-positive and whether Pluvicto could help me?
• How much can Pluvicto slow my cancer compared to standard treatment alone?
• Is the benefit worth the side effects and extra visits for treatment?
• Should Pluvicto be used early, when my cancer still responds to hormone therapy, or later?
• How will my doctor decide the best time to start it?
• Can the number of treatments be adjusted based on how I respond?
• Will Pluvicto be given alongside hormone therapy, chemotherapy, or other medications?
• Could Pluvicto help me live longer, or just slow the cancer’s growth?
• How much will it cost, and is it covered by insurance?
• What benefits have been proven?
• What questions are still being researched before Pluvicto becomes a standard treatment for all patients?

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