Baptist Health Miami Cancer Institute is among the first cancer centers in the region to offer an innovative radiopharmaceutical therapy that can extend survival and increase quality of life for patients with stage 4 metastatic prostate cancer, according to radiation oncologist Adeel Kaiser, M.D. 

PluvictoTM (lutetium Lu 177 vipivotide tetraxetan), a radiopharmaceutical, was approved in 2022 by the U.S. Food and Drug Administration (FDA) “for the treatment of adult patients with prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer (PSMA-positive mCRPC) that has spread to other parts of the body.”

Miami Cancer Institute, part of Baptist Health Cancer Care, was among the first in South Florida to receive Pluvicto and has been treating late-stage prostate cancer patients with the drug, which Dr. Kaiser says is administered via a series of six injections given six weeks apart

At some point almost all metastatic prostate cancer patients will experience a rise in their prostate-specific antigen (PSA) level with imaging evidence of disease progression despite multiple rounds of drug therapies, including hormonal and chemotherapy agents. These patients may now benefit from Pluvicto,” says Dr. Kaiser, who is an expert in the use of the drug.

Black men have much higher risk for prostate cancer

Prostate cancer is the second most common cancer in men, according to 2023 data from the American Cancer Society (ACS). Nearly 300,000 new cases are expected to be diagnosed this year, with roughly 35,250 of those expected to be fatal.

The ACS notes that the number of prostate cancers diagnosed each year declined sharply from 2007 to 2014, “coinciding with fewer men being screened because of changes in screening recommendations.” Since 2014, however, the incidence rate has increased by 3 percent per year overall and by about 5 percent per year for advanced-stage prostate cancer.

Also concerning is the fact that Black men are 70 percent more likely than white men to be diagnosed with prostate cancer and two to four times more likely than other racial and ethnic groups to die from the disease, according to the ACS.

Clinical trial paves way for new therapy

In a high-profile 2021 study (VISION Trial) reported in the New England Journal of Medicine, researchers tested the new therapy on a select group of patients with metastatic (incurable) prostate cancer, Dr. Kaiser says. They leveraged a new imaging technology using a radiopharmaceutical, or a radioactive tracer, bound to the prostate-specific membrane antigen (PSMA) molecule found on the surface of cancer cells.

“In general, the more aggressive the cancer, the more PMSA is found on the cell surface,” Dr. Kaiser explains. “PSMA is over-expressed in prostate cancer cells, especially those left behind after multiple rounds of systemic therapies.”

To better understand how Pluvicto therapy developed, Dr. Kaiser points to the development of positron emission tomography (PET) imaging for prostate cancer. “Over the last two decades researchers have worked tirelessly to develop molecules that could be attached to a radioactive, positron emitting isotope to visualize various solid tumors,” he says. “Many cancers overutilize glycolysis for energy, and so fluorodeoxyglucose (FDG) was developed to visualize these.”

Unfortunately, Dr. Kaiser says, prostate cancers were not well visualized with FDG and another agent was needed, which led to the development of a molecule targeting PSMA. This dramatically improved the ability of clinicians to accurately visualize metastatic deposits from prostate cancer, he says.

In the VISION Trial, Dr. Kaiser explains, researchers sought to answer the question, “If we’re already using radiopharmaceuticals to visualize cancer cells, why can’t we use the same principle to attach a radioactive molecule that could deliver lethal doses of radiation to those same PSMA expressing tumor cells?”

Increasing survival time by more than 35 percent

The Phase 3 study compared two groups of patients with metastatic prostate cancer: one that received standard therapies for stage 4 disease, and one that received those same standard therapies with the addition of Pluvicto.

According to Dr. Kaiser, the study showed that patients in the second group were able to improve survival by four months on average. “Pluvicto extended average survival time from 11.3 months to 15.3 months,” he says. “I know that doesn’t sound like much but that’s an increase of more than 35 percent.”

Dr. Kaiser noted that Pluvicto not only reduces the amount of cancer, it also decreases the negative effects of cancer, such as pain. “It offers patients with late-stage disease extended survival and a better quality of life,” he says.

Of the patients participating in the VISION trial who received standard therapies without Pluvicto, 36 percent reported serious side effects, Dr. Kaiser says, compared to 50 percent for those who did receive the drug. “So, we’re looking at 14 percent additional toxicity compared to normal for stage 4 patients. Given the chance to extend their survival time and quality of life, that’s a trade-off I think many patients would be willing to make,” Dr. Kaiser says.

Some men not candidates for Pluvicto

Unfortunately, Dr. Kaiser cautions, Pluvicto isn’t for everyone. “It isn’t intended for patients with curative cancers that can be treated with external radiation, proton therapy, surgery or other therapies,” he says. “It is used only for those with late-stage prostate cancer who have already exhausted all other anti-cancer treatments.”

In addition, he says, some patients who have undergone prior anti-cancer therapies, especially chemotherapy, may not be candidates because they have depleted bone marrow reserves. “As a result, they may have low blood counts below the thresholds permissible for administering Pluvicto.”

Increased demand, supply chain issues impacted availability

Shortly after the VISION trial was published, there was a sudden, high demand for Pluvicto, according to Dr. Kaiser, and Miami Cancer Institute was immediately booked for weeks in advance for this treatment. At the same time, supply chain challenges limited the drug’s availability.

“Prostate cancer is the second most common cancer among men worldwide, after all, and many men with metastatic cancer will eventually run out of effective treatment options,” Dr. Kaiser notes. “However, those supply chain issues have now been resolved with the recent FDA approval of U.S. production sites.”

New trial studies effects of upfront treatment with Pluvicto

Dr. Kaiser reports that Miami Cancer Institute has been very involved in research investigating Pluvicto and other lutetium agents targeting prostate cancer. “We were actively enrolling patients for the PSMAAddition trial examining upfront Pluvicto usage at the initial diagnosis of metastatic prostate cancer,” he says of the trial, which is now closed to accrual with data forthcoming.

As with all cancer drug trials, Dr. Kaiser says the objective is to see how it does on the sickest patients first. “They’re the ones who stand to benefit the most from this drug. And if it proves to be beneficial, then you can start investigating its impact earlier in the treatment course.”

Researchers at Miami Cancer Institute are also launching a clinical trial examining lutetium-based therapy in combination with niraparib, an established drug for prostate cancer. The trial is being led by medical oncologist Rohan Garje, M.D., the Institute’s chief of genitourinary medical oncology.

“We’re also exploring other concepts to expand the indications for Pluvicto-style lutetium-based therapy for prostate cancer patients, who, at present, do not qualify for Pluvicto,” Dr. Kaiser says, adding that the drug has the potential to benefit a lot of people. “So many patients will end up as stage 4 in their cancer journey,” he says. “For patients at this stage, Pluvicto is the most effective strategy we have now. It allows us to treat the cancer more effectively.”