Pluvicto: A Targeted Radiation Breakthrough For Advanced Prostate Cancer

To truly understand the significance of Pluvicto (lutetium Lu 177 vipivotide tetraxetan), it’s helpful to know a little about metastatic castration-resistant prostate cancer, or mCRPC. When prostate cancer is advanced, it often spreads beyond the prostate to other parts of the body, like the bones or lymph nodes. This is what we call “metastatic” cancer.

A common first step in treating advanced prostate cancer is hormone therapy, also known as androgen deprivation therapy (ADT). This treatment aims to lower or block testosterone, which fuels the growth of most prostate cancer cells. Hormone therapy can be incredibly effective, often slowing or halting the disease’s progression for many months or even years.

However, for many patients, the cancer eventually becomes “castration-resistant. This means that even with very low levels of testosterone, the cancer finds ways to continue growing and spreading. When this happens, it becomes mCRPC. This stage of the disease can be particularly challenging to treat, as it has become more aggressive and requires different strategies beyond initial hormone therapy. Patients facing mCRPC often experience symptoms that impair their quality of life, which underscores the urgent need for effective new treatments.

Historically, after hormone therapy, options might include chemotherapy or switching to a different type of hormone therapy. While these are vital tools in the fight against cancer, chemotherapy, in particular, can come with significant side effects that can negatively impact daily life, leading many patients and their doctors to prefer to delay or avoid it if possible. This is where a targeted therapy like Pluvicto offers a compelling new alternative.

Radioligand Therapy: A Targeted Approach

Pluvicto belongs to a class of treatments called radioligand therapy, or RLT. Think of RLT as a highly sophisticated, guided missile system designed to target and destroy cancer cells while leaving healthy tissues largely untouched.

“Radiopharmaceuticals are a newer category of medication. This class of medications works by bringing a radiation molecule to the target site, and every drug option has a different target,” explains Dr. Yen.

Here’s a breakdown of how it works:

• The Ligand: Scientists design a special molecule, called a “ligand,” that has a unique ability to seek out and attach to certain proteins found mostly on the surface of cancer cells. For prostate cancer, this target protein is called Prostate-Specific Membrane Antigen, or PSMA.
• The Radioactive Isotope: This molecule is then chemically linked to a tiny amount of a radioactive substance, or “isotope.” Together, they form what’s called a “radioligand.”
• Targeted Delivery: Once this radioligand is injected into your bloodstream, it travels throughout your body. Because the ligand is specifically designed to bind to PSMA, it largely bypasses healthy cells and hones in on the cancer cells that express this protein.
• Precise Radiation Delivery: When the radioligand latches onto the cancer cell, the attached radioactive isotope releases a small, localized dose of radiation. This radiation damages the DNA of the nearby cancer cells, ultimately causing them to die.

This dual-action approach means that the radiation is delivered with incredible precision, minimizing damage to surrounding healthy tissue. This is a key advantage, as it often leads to fewer and milder side effects compared to traditional, more widespread radiation or chemotherapy treatments.

Am I Eligible For Pluvicto?

Lutetium Lu 177 vipivotide tetraxetan, which is known by the brand name Pluvicto, is an innovative intravenous radioligand therapy specifically designed for patients with PSMA-positive mCRPC.

It is the first and only targeted radioligand therapy for patients with PSMA-positive mCRPC before the need for chemotherapy, marking a significant advancement in treatment options.

“The PSMAfore study has looked at [Pluvicto] in the pre-chemotherapy setting, and again, it’s been FDA approved in that setting as well. So you could be utilizing it in patients after chemotherapy or before chemotherapy, as long as they have metastatic castration-resistant prostate cancer,” says Dr. Yen.

Pluvicto is FDA-approved for adults with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Specifically, Pluvicto is indicated for patients who:

• Have a confirmed diagnosis of PSMA-positive mCRPC
• Have already been treated with an androgen receptor pathway inhibitor (ARPI) therapy

And, importantly, they are considered appropriate to delay taxane-based chemotherapy. This means that for many patients who wish to defer or avoid chemotherapy due to its side effects, Pluvicto now offers an effective alternative earlier than before. Previously, it was only approved after both hormone therapy and chemotherapy.

Before treatment, a crucial step is undergoing a PSMA PET scan. This scan uses a small amount of a different radioactive substance (gallium-68 gozetotide, or Locametz) that also binds to PSMA. This helps your doctor “see” where the cancer has spread and, most importantly, confirms that your cancer cells express enough PSMA. Although the FDA only approved 68Ga gozetotide PET imaging, there is an alternative (Pylarify, F-18 Piflufolastat), which is also permitted by the NCCN guidelines.

If the cancer cells “light up” on this scan, it indicates they will also bind to Pluvicto, making you a potential candidate for this targeted therapy.

The PSMAfore Trial: Understanding The Data

The expanded approval for Pluvicto is based on the results from a clinical trial called PSMAfore. This Phase III trial involved 468 patients with PSMA-positive mCRPC who had already progressed on one ARPI therapy and whose doctors considered them appropriate to delay chemotherapy.

The findings from PSMAfore, listed below, were highly encouraging and brought a renewed sense of hope.

• Significant Delay in Disease Progression: Pluvicto significantly reduced the risk of radiographic progression (meaning the cancer growing or spreading) or death by 59% compared to a change in ARPI therapy. This is a profound difference, showing that Pluvicto is more effective at controlling the disease’s advancement.
• More Time Without Progression: The study also showed that Pluvicto more than doubled the median radiographic progression-free survival (rPFS), which is the time patients lived without their cancer progressing visibly on scans. Patients treated with Pluvicto had a median rPFS of 11.6 months, compared to 5.6 months for those who received a change in ARPI. This means more time living well, with the disease under control.
• Tumor Shrinkage: Beyond delaying progression, Pluvicto also demonstrated its ability to shrink or even make tumors disappear. Approximately 49% of patients on Pluvicto saw their tumors shrink or disappear, compared to 14% with a second hormone therapy.
• Improved Quality of Life: Importantly, Pluvicto was shown to maintain or improve patients’ health-related quality of life, including delaying the worsening of pain symptoms. This is vital because, for many patients, feeling better and maintaining their daily activities is just as important as extending life.

These results led to the approval of this drug earlier in the treatment course for patients with mCRPC.

What To Expect During Treatment

Beginning a new therapy can bring a mix of emotions, from hope to apprehension. Knowing what to expect can help ease some of those concerns.

Pluvicto is given as an intravenous (IV) infusion, meaning it’s delivered directly into your bloodstream through a vein, typically in your arm. The injection itself usually only takes a few minutes. After the infusion, there’s typically a period of observation for one to two hours, and then patients can go home.

The treatment plan usually involves up to six doses, given once every six weeks. Your care team will monitor your progress closely, and if you are responding well and tolerating the treatment, it will continue.

You typically don’t need to fast or do any special preparations before receiving the diagnostic imaging or the treatment infusion. Your medical team will provide all the necessary supportive care.

Your care team will monitor your blood cell counts regularly (typically every three weeks) as they can temporarily dip during treatment, though this is usually not symptomatic. They will also keep a close eye on your kidney function and overall health.

Radiation Safety Precautions

Because Pluvicto involves a radioactive isotope, certain radiation safety precautions are important to protect those around you, especially children and pregnant women.

Your care team will provide you with specific instructions, but general guidance includes:

• Maintaining physical distance from others for a few days after each dose
• Flushing the toilet twice after each use and practicing good hygiene
• Staying well-hydrated helps your body flush out the radioactive material

These precautions are temporary and crucial for the safety of your loved ones, allowing the radioisotope to naturally leave your body.

Potential Side Effects

Like any cancer treatment, Pluvicto can have side effects, though they are generally considered milder than those associated with conventional chemotherapy. It has a favorable safety profile.

“Side effects of Pluvicto, in general, depend on the radiation and where the medication goes,” Dr. Yen explains. “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.”

Common side effects can include:

• Dry mouth (xerostomia)
• Feeling tired or low on energy (fatigue)
• Stomach upset
• Constipation or mild diarrhea
• Decreased appetite
• Anemia (low red blood cell count) or low white blood cell count
• Arthralgia (joint pain) or back pain

In some cases, more serious side effects such as bone marrow suppression or kidney problems may occur, especially in patients with pre-existing conditions. This is why regular monitoring and open communication with your healthcare team are so important throughout your treatment journey.

Questions To Ask Your Doctor

• Am I eligible for treatment with Pluvicto?
• Can I undergo a PSMA PET scan to determine if my cancer is PSMA-positive?
• What are the specific risks and benefits of Pluvicto for my individual situation?
• How does Pluvicto compare to other treatment options available to me at this stage?
• What precautions should I take before and after receiving Pluvicto to ensure safety for myself and my family?
• What kind of support will be available to me throughout my treatment journey?

Content independently created by SurvivorNet with support from Novartis Pharmaceuticals Corp.

Learn more about SurvivorNet's rigorous medical review process.

---