BY PAM MCGRATH

Men with prostate cancer that has metastasized, spreading to other parts of the body, now have a new treatment option available to them that, though not lifesaving, can offer a better quality of life. Approved by the Food and Drug Administration (FDA) in 2022, a drug, called lutetium Lu 177 vipivotide, or Pluvicto, may be used in patients for whom other available treatments did not work or became ineffective.

Jeff Michalski, MD, Washington University radiation oncologist, notes that this treatment is considered for men with metastatic prostate cancer that continues to grow, even when testosterone is reduced to very low levels. Michalski, who treats patients at Siteman Cancer Center, based at Barnes-Jewish Hospital and Washington University School of Medicine, says candidates must also have what is known as PSMA-positive cancer. PSMA, or prostate specific membrane antigent, is a protein found mainly on the surface of prostate cells; levels of PSMA are highly elevated on prostate cancer cells compared to normal prostate cells. “We use this drug to treat people with metastatic cancer whose disease continues to progress even after receiving hormone therapy and chemotherapy,” Michalski adds.

“Pluvicto and other similar drugs currently under investigation use radioactive molecules that can specifically bind to the PSMA found on the surface of prostate cancer cells,” says Russell Pachynski, MD, Washington University medical oncologist at Siteman. “Known as a targeted treatment, the drug is designed to seek out, bind to and kill only cells that express PSMA.”

To be considered for treatment with this new drug, patients at Barnes-Jewish Hospital undergo a series of scans and tests that assess overall health and consider several factors, including kidney function. One of the tests, a scan called positron emission tomography, or PET, can reveal where prostate cancer has metastasized in the body. “About 10% of patients have metastatic cancer that does not express PSMA, so the PET scan is an important first step in identifying patients who will benefit from the treatment,” says Michalski.

KNOWN AS A TARGETED TREATMENT, THE DRUG IS DESIGNED TO SEEK OUT, BIND TO AND KILL ONLY CELLS THAT EXPRESS PSMA.

Once cleared for treatment, patients receive an intravenous injection of the drug every six weeks for a total of six doses, provided that blood counts, kidney function and overall health remain stable. “The majority of patients tolerate this treatment very well,” says Michalski. “The most common side effects are dry eyes and dry mouth, and patients with significant metastatic disease may experience nausea. But those are relatively rare instances.”

During treatment, patients are closely monitored, including receiving additional scans. Vikas Prasad, MD, Washington University nuclear medicine specialist with the university’s Mallinckrodt Institute of Radiology, notes that a scan taken immediately after therapy can identify distribution of the drug and can help calculate the optimal dosage for future treatments.

Pachynski says this new PSMA-targeting therapy falls under the umbrella of palliative care for people with metastatic prostate cancer. “It is not a cure for the disease, but it has proven to reduce symptoms affecting quality of life, and it has extended life,” he says. “This is a major advance in our ability to treat people with advanced-stage prostate cancer because it represents a new class of therapeutics that is now FDA-approved and more widely available.” Similar drugs are currently in development, he adds.

Prasad says that very few patients are “super-responders,” meaning they experience decreases in the size and number of metastases and decreases in PSA levels after taking the drug. PSA, or prostate-specific antigen, is found in the blood; high levels of PSA may be an indication of prostate cancer. “Although the number of patients experiencing these dramatic responses is very low, we’re studying their results. We want to know why some people respond extremely well and others don’t. The answers will help us further refine treatment.”

Researchers at Washington University School of Medicine participated in the VISION phase 3 clinical trial that led to the FDA’s approval of lutetium Lu 177 vipivotide. Subsequently, university researchers participated in trials that tested the drug in earlier stages of prostate cancer to determine its effectiveness in reducing the spread of the disease.

“This approach to treating prostate cancer requires a multidisciplinary team that includes radiation oncologists, nuclear medicine physicians and medical oncologists, among others,” says Michalski. “Working together, we provide coordinated care that results in patients receiving treatment effectively, efficiently and safely.”