Expanding the Use of Targeted Therapy Pluvicto: New FDA Approval Brings Hope for Advanced Prostate Cancer

This is a major step forward. Until now, Pluvicto was only available for patients who had already undergone chemotherapy. Now, it can be used earlier — before chemo is required — tripling the number of eligible patients and giving many more men the chance to access this innovative therapy. Trial data showed using Pluvicto in this setting reduced the risk of disease progression or death by 59% compared to switching to another hormone therapy.

However, it’s important to note that this new therapy is not for newly diagnosed localized prostate cancer.

“I think is important for your viewers and your audience to hear. I do get many inquiries for patients who’ve just been diagnosed with localized prostate cancer who are looking for an alternative to either definitive therapy with surgery or definitive therapy with radiation and asking whether Pluvicto would serve that role,” Dr. Michael Morris, a leading prostate cancer expert at Memorial Sloan Kettering Cancer Center, tells SurvivorNet.

“It does not have a role right now in serving [these patients]. So go ahead and get primary therapy with curative intent for localized disease with the standard and traditional modalities.”

What is Pluvicto?

Pluvicto is part of a newer class of targeted cancer therapies called radioligand therapies (RLTs). It delivers a small but powerful dose of radiation directly to prostate cancer cells that express a protein known as PSMA (prostate-specific membrane antigen). This protein is found on most prostate cancer cells but not on normal tissues — making it a valuable target for treatment.

Before receiving Pluvicto, patients must undergo a PSMA PET scan using an approved imaging agent, such as Locametz, to confirm that their cancer cells express PSMA.

This treatment is now approved for men with mCRPC — which means the cancer has spread beyond the prostate and is no longer responding to hormone therapy — who have already been treated with one ARPI (like abiraterone or enzalutamide) and who are not yet ready for chemotherapy.

For many men and their families, this offers a new option at a critical point in the treatment journey.

How Does Pluvicto Work?

Pluvicto is designed to seek out and bind to cancer cells that express PSMA. Once attached, it delivers a small, targeted dose of radiation directly to the cancer cells — killing them while minimizing damage to surrounding healthy tissues.

This approach, sometimes called a “theranostic” (therapy + diagnostic), uses the power of precision medicine to both detect and treat cancer in a personalized way.

“This approval is a significant step forward and should open the doorway to a therapy that has clear clinical advantages for the patient with mCRPC who has progressed on one ARPI and has not received chemotherapy,” adds Dr. Morris.

What Did the Clinical Trial Show?

The FDA approval is based on results from the Phase III PSMAfore clinical trial, which enrolled 468 patients with PSMA-positive mCRPC. All had previously received an ARPI, and their cancer had continued to grow. Patients in the study were randomly assigned to receive either Pluvicto or switch to another ARPI.

Here’s what the study found:

• Pluvicto reduced the risk of disease progression or death by 59% compared to switching to another hormone therapy.
• It more than doubled the median time patients lived without disease worsening (11.6 months vs. 5.6 months).
• Patients receiving Pluvicto maintained a better quality of life, with longer periods before pain or physical functioning worsened.
• Overall survival (how long patients lived) was similar between groups, but nearly 60% of patients in the control group eventually crossed over to Pluvicto after their cancer progressed, making it harder to measure a survival difference.

These results highlight Pluvicto’s ability to delay cancer progression, improve comfort, and give patients more time before needing chemotherapy.

Side Effects of Pluvicto

Dr. Morris points out that Pluvicto is a great alternative to chemotherapy — and may reduce the side effects patients experience.

“You can now position Pluvicto before chemotherapy. You can position it after chemotherapy, and the side effect profile is reasonable so that putting it in the pre chemotherapy context is quite medically appropriate,” he explains.

Still, like all treatments, Pluvicto can cause side effects. In the trial, most were mild to moderate.

Potential side effects include:

• Dry mouth
• Fatigue
• Nausea
• Constipation
• Decreased appetite
• Anemia

There are also potential risks associated with radiation exposure, low blood counts (myelosuppression), and kidney effects, so your doctor will monitor you closely throughout treatment.

Still, the treatment was generally well-tolerated, and importantly, did not impair the ability to receive chemotherapy later if needed.

Why This Approval Matters

Roughly 35,000 men die of prostate cancer each year in the U.S., and that number is growing. Many men with mCRPC do not live long enough to receive multiple lines of therapy — making it crucial to use effective treatments earlier in the disease course.

For years, patients and their families have faced limited options and uncertain outcomes and this approval gives patients more control earlier in their treatment journey.

Questions To Ask Your Doctor

• Do I have PSMA-positive prostate cancer?
• Have I received an androgen receptor pathway inhibitor?
• Am I eligible to receive Pluvicto now, before chemotherapy?
• What are the benefits and risks of this treatment?
• How will we monitor if it’s working?

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