Breakthrough nuclear medicine treatment helps patients with advanced prostate cancer

Patients with metastatic castration-resistant prostate cancer (mCRPC) often fail conventional treatments, including surgery, radiation therapy, hormone therapy, chemotherapy and previously limited nuclear medicine treatment options. In March 2022, the FDA approved a new nuclear medicine treatment that uses radiopharmaceutical Pluvicto, which targets prostate-specific membrane antigen (PSMA) on prostate cancer cells and was shown to give some patients additional months of improved quality of life.¹

“Pluvicto is introduced at the end of a chain of therapeutic options that are beginning to fail,” said Dr. Mark Tulchinsky, associate director of nuclear medicine at Penn State Health Milton S. Hershey Medical Center and a professor of radiology and medicine at Penn State College of Medicine. “It becomes a powerful new barrier, stopping cancer from growing and spreading. In many cases, Pluvicto decreases the volume of metastatic prostate cancer in the body. If not for this new therapy, these patients might experience unfortunate complications caused by growing tumors, such as suffering from pain and disabilities.”

In July 2022, following more than a year of preparation by Tulchinsky and members of a multidisciplinary Genitourinary cancer disease group co-led by Dr. Monika Joshi, a prostate cancer expert and Dr. Matthew Kaag, clinical program co-leader in genitourinary oncology, Penn State Cancer Institute became one of the first three cancer centers in Pennsylvania to start administering Pluvicto.

Because of the high demand for this treatment across the country and limited supply, no other health care centers in Pennsylvania will administer Pluvicto for now.

VISION trial results

Pluvicto is a “theranostic” treatment, one that combines the strengths of diagnostic techniques with those of therapeutic nuclear medicine. The U.S. Food and Drug Administration (FDA) designated it as a breakthrough drug for accelerated approval.

The approvals were based on the phase 3 VISION trial results published in the New England Journal of Medicine. The trial included 831 patients with mCRPC who had previously received androgen receptor pathway inhibitor therapy and taxane-based chemotherapy. The research also demonstrated the PSMA target on the tumor can be effectively detected using the Locametz scan. Researchers followed the participants for a median of 20.9 months, gaining conclusive results.

All patients were continued on a standard of care, while two-thirds were randomly selected to also receive Pluvicto.¹ Compared with patients who received standard of care alone, patients who received Pluvicto demonstrated a significantly better imaging-based progression-free survival (8.7 months versus 3.4 months) and overall survival (15.3 months versus 11.3 months).¹

“For me, the most encouraging finding from the VISION trial was how often Pluvicto was able to deter this aggressive and already advanced tumor from continuous growth or even clear it from a patient’s body,” Tulchinsky said. “More than half of patients receiving Pluvicto either cleared cancer completely or shrunk it. None of the patients receiving only the standard of care showed tumor disappearance and only 3% showed some tumor shrinkage.”

Tulchinsky said Pluvicto has the ability to extend life by several months while keeping patients more functional, which is most uplifting for patients. He recalls patients’ excitement when they learned about the Pluvicto outpatient therapy and shared their plans to spend more time with loved ones and pursue activities they enjoy.

Patient selection using theranostics

To select patients who may benefit from Pluvicto, clinicians use Locametz scans that can show whether patients’ tumors are PSMA-positive. The diagnostic agent Locametz is aimed at the same target as the treatment agent Pluvicto. The use of imaging agents aimed at the PSMA target, such as Locametz, is a logical approach to identifying patients who may benefit from Pluvicto. This approach is called theranostics and is poised to advance nuclear medicine therapies to achieve more significant results in prostate cancer and other malignancies.

“Fusing diagnostic and therapeutic capabilities into a theranostic approach enables us first to see whether a patient has the targets we’re looking for, and then send the therapeutic agent after those targets that we can see on the diagnostic image,” Tulchinsky said. “We then have much greater assurance that the Pluvicto therapy will be successful. This allows for the individualization of therapeutic management.”

Following a PET-CT scan using Locametz, nuclear medicine physicians can interpret the findings on the same day and share them with patients and their families during a consultation. If the Locametz results support proceeding with Pluvicto therapy, the nuclear medicine physician can approve that patient for Pluvicto therapy during the visit. If the patient wishes to proceed, their first treatment at Penn State Cancer Institute can be set up for the earliest available date.

Reducing the burden of treatment

Administration of Pluvicto treatment is straightforward when done by a trained nuclear medicine technologist. Compared with the side effects of typical chemotherapies used for advanced cancers, Pluvicto is generally well tolerated by most patients.

“When patients arrive for an infusion, we take vital signs and place two IV catheters, one in each arm,” said Jessica Meley, chief nuclear medicine technologist in the Department of Radiology at Penn State Health. “We use one catheter to deliver Pluvicto and the other to administer hydrating fluids and other medications. We infuse Pluvicto for five minutes and then take vital signs 30 minutes later. The treatment takes about two hours from start to finish.”

Patients receive six such infusions, spaced six weeks apart, which makes it a convenient regimen for most patients.

“The majority of patients experience little discomfort and few side effects,” Tulchinsky said. “The side effect profile is relatively well tolerated. Not only is Pluvicto effective where other treatments have failed, but it’s also much less burdensome and allows most patients to maintain their well-being through the treatment course.”

Potential future applications

Two phase 3 trials are investigating how Pluvicto could potentially benefit more patients at earlier stages of prostate cancer.

The PSMAfore trial is studying the treatment’s potential effect on image-based, progression-free survival in patients with mCRPC who have not received taxane-based chemotherapy. The trial is assessing whether Pluvicto therapy can be as effective as a change in androgen receptor pathway inhibitor.²

The PSMAddition trial, for which Penn State Cancer Institute is recruiting participants, is investigating the safety and efficacy of Pluvicto plus standard of care compared with standard of care alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC).³ Unlike mCRPC, patients with mHSPC are in a significantly earlier stage of cancer.

Tulchinsky is excited about investigating the potential of Pluvicto to treat prostate cancer at much earlier stages. He predicts that in the next decade, nuclear medicine physicians will be able to use theranostics at an even higher technical level that should enable determining individualized dosages depending on the size, accumulation and retention of the drug in the cancer metastases.

The predicted developments will allow physicians to deliver Pluvicto and other radiopharmaceuticals with even greater individualization and expected effectiveness. In the meantime, Tulchinsky anticipates eventually administering Pluvicto to up to six patients per week.

“I hope other physicians will recognize Pluvicto as a pivotal therapy that not only has a relatively low burden of side effects and patient inconvenience but also improves lives despite an advanced prostate cancer diagnosis,” Tulchinsky said. “This is a sophisticated and effective treatment approach that health care providers at Penn State Health are committed to making available to as many appropriately selected patients as possible and as promptly as possible.”

Tulchinsky commended the members of the Genitourinary Tumor Board for their efforts to bring this novel therapy to Penn State Cancer Institute. “This teamwork could not have succeeded without the strong support of the Department of Radiology leadership, including the chair, Dr. Timothy Mosher, and the chief of nuclear medicine, Dr. Thomas Allen,” he said.

References:

1. Sartor O, de Bono J, Chi KN et al. Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021;385:1091-1103, doi:10.1056/NEJMoa2107322.
2. Sartor OA, Morris MJ, Chi KN et al. PSMAfore: A phase 3 study to compare ¹⁷⁷Lu-PSMA-617 treatment with a change in androgen receptor pathway inhibitor in taxane-naïve patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2022;40(6). doi:10.1200/JCO.2022.40.6_suppl.TPS211.
3. Sartor OA, Tagawa ST, Saad F et al. PSMAddition: A phase 3 trial to compare treatment with ¹⁷⁷Lu-PSMA-617 plus standard of care (SOC) versus SOC alone in patients with metastatic hormone-resistant prostate cancer. J Clin Oncol. 2022;40(6). doi:10.1200/JCO.2022.40.6_suppl.TPS210.