Prostate cancer treatment options in Korea have been strengthened this year.
Pluvicto (lutetium vipivotide tetraxetan), a radioisotope treatment introduced in May this year as a last resort treatment for prostate cancer patients, has recently been used in earnest at university hospitals.
“In hormone-resistant metastatic prostate cancer, androgen receptor pathway blockade therapy and taxane-based chemotherapy were the main treatment options, but patients who progress despite these treatments had no further treatment options,” said Professor Lee Dong-yun of the Department of Nuclear Medicine at Asan Medical Center on the YouTube channel “Asan Medical Center.”
Pluvicto is a treatment that is emerging as a new hope for hormone-resistant metastatic cancer that has exhausted all treatment options, Professor Lee said.
Among prostate cancer drugs, Pluvicto is a new concept. “It is a personalized radioisotope therapy that emits a beta ray called lutetium (177-Lu) to kill cancer cells and has fewer side effects than other chemotherapy treatments,” Lee explained.
However, not all hormone-resistant metastatic prostate cancer patients with no further treatment options can be treated with Pluvicto.
“The current treatment is only indicated for adult patients with prostate-specific membrane antigen-positive (PSMA-positive) hormone-resistant metastatic prostate cancer who have previously received androgen receptor pathway blocking therapy (enzalutamide, abiraterone, etc.) and taxane-based chemotherapy (docetaxel, carbazitaxel),” Lee said.
Unlike standard antihormonal or chemotherapy treatments, which are broadly curative, personalized radioisotope therapy, as it is called, can be tailored based on how much of a prostate-specific membrane antigen called PSMA is expressed on cancer cells.
PSMA is expressed to some degree in normal prostate cells. However, it is strongly associated with prostate cancer growth, and its expression is known to increase in localized and metastatic lesions, depending on the cancer's grade and hormone resistance status.
Patients with hormone-resistant metastatic prostate cancer who have exhausted conventional treatment options should undergo one imaging test to determine if they are candidates for treatment with Pluvicto.
“The primary way to determine the presence of PSMA expression, which is essential for eligibility for Pluvicto, is to perform a prostate cancer-specific PET-CT scan,” Professor Lee said. “The injection of gallium-68 PSMA-11, which combines a diagnostic radioisotope, gallium-68 (Ga-68), with a substance called PSMA-11 that targets PSMA expressed on prostate cancer cells, results in significantly increased binding and accumulation of gallium-68 PSMA-11 in prostate cancer lesions with high levels of PSMA compared to normal tissue, which can be imaged and diagnosed by PET-CT.”
Patients considered for treatment with Pluvicto should undergo a gallium-68 PSMA-11 PET-CT within three months of their treatment date. Higher prostate-specific membrane antigen expression is expected to result in better treatment outcomes with Pluvicto.
“When screened patients are given Pluvicto, which combines PSMA-617, which targets PSMA, with tutecium-177, a therapeutic radioisotope that destroys cancer cells, it binds to recurrent and metastatic prostate cancer lesions that express PSMA, providing a cancer cell-targeted treatment, and does not reach normal cells that do not express PSMA, resulting in fewer side effects than other cancer treatments,” Lee said.
Patients with hormone-resistant metastatic prostate cancer that expresses PSMA may not be able to be treated due to their physical condition. Inadequate bone marrow function (hematopoiesis - the production of red blood cells, white blood cells, neutrophils, and platelets), renal (kidney) function, and liver function make it difficult to treat patients with Pluvicto. It is also difficult when patients are in poor systemic condition due to internal or external medical problems, including acute infections.
There is one more barrier to treatment: Cost.
“Pluvicto is an uncompensated and expensive drug that costs about 37 million won ($25,170) for a single treatment,” Professor Lee said. “It puts a lot of cost burden on patients. I think an institutional device that can increase patient accessibility will be needed in the future.”
Actinium-based radiopharmaceuticals and lower-cost radiopharmaceuticals draw expectation
The number of treatment options for prostate cancer is expected to increase in the future. First, research is underway to expand Pluvicto's therapeutic applications, which will allow it to be used at earlier stages of the disease.
“Currently, Pluvicto is indicated for hormone-resistant metastatic prostate cancer, but many clinical studies are being conducted around the world to expand its therapeutic indications. Notably, global clinical trials are underway to explore the application of personalized radioisotope therapy in the early-stage spectrum, including hormone-resistant metastatic prostate cancer,” Professor Lee noted.
“If meaningful results are achieved in this patient population, we believe that targeted radiopharmaceuticals will become an indispensable option at all stages of the treatment of patients with metastatic prostate cancer,” he added.
In addition to the beta-agonist Lutetium, experts are also looking forward to the introduction of the more potent alpha-agonist Actinium (Ac-225).
“Clinical studies using an alpha-emitting radioisotope called actinium, which has slightly higher energy and fewer side effects than beta-emitting radiation, will be conducted soon,” Lee said. “There is a positive outlook that alpha-emitting radiopharmaceuticals will emerge as another powerful option for patients who have failed lutetium therapy.”
Access to radiopharmaceutical treatment for prostate cancer is also likely to improve in the future.
“As Korean pharma companies are also expected to launch radioisotope drugs, we expect the market for radiopharmaceuticals with various options that can fully consider cost-effectiveness aspects such as price competitiveness to be formed shortly,” Lee said.