What this means for patients: Today, the therapy 177lutetium-PSMA-617 (Lu-PSMA; trade name Pluvicto®) was approved by the FDA for patients with advanced (metastatic) prostate cancer who have been treated with androgen receptor pathway inhibitor therapy. This medicine delivers a small dose of radiation attached to a molecule that specifically binds to prostate cancer cells. It has been shown to slow disease progression and maintain quality of life in patients with advanced prostate cancer.
If you have advanced prostate cancer, speak with your doctor about treatment options and additional tests that might help guide your treatment.
Dr. Oliver Sartor, Director of Radiopharmaceutical Clinical Trials at Mayo Clinic Comprehensive Cancer Center, speaks with Dr. Zachary Klaassen of the Georgia Cancer Center about the new approval and what it means for patients in this video.
The FDA approval of 177Lutetium-PSMA-617 (Lu-PSMA) is now expanded to patients with metastatic castration-resistant prostate cancer (mCRPC) who have received an androgen receptor pathway inhibitor (ARPI, such as abiraterone or enzalutamide), and who are considered appropriate to delay taxane-based chemotherapy (such as docetaxel). Patients must also have a positive PSMA PET scan. This means that the therapy can be used earlier in the course of prostate cancer (i.e., before chemotherapy) and is hopeful news for patients who have seen their disease progress on an ARPI.
Approval was based on the large, randomized international Phase 3 PSMAfore trial. Included patients had mCRPC whose disease had worsened on an ARPI. This study compared treatment with Lu-PSMA vs. a change in ARPI medication (abiraterone or enzalutamide) The results showed that Lu-PSMA reduces disease progression compared with changing ARPI. Patients treated with Lu-PSMA were 59% less likely to have their disease worsen on scans or die. The FDA announcement notes a small increase in overall survival with Lu-PSMA. Lu-PSMA patients had more stable quality of life: they had a longer time to worsening pain, functioning, and well-being. Serious side effects were less common in the Lu-PSMA group, though certain specific symptoms such as dry mouth and nausea were more common.
Lu-PSMA works to deliver a small amount of radiation to prostate cancer cells anywhere in the body. One part of the Lu-PSMA molecule recognizes and binds to its target, called PSMA (prostate-specific membrane antigen). PSMA is a protein that is present on nearly all prostate cancer cells but not on most normal tissue. This PSMA-seeking “arrow” is chemically linked to a radioactive “payload” called lutetium-177. When Lu-PSMA binds to the prostate cancer cell, the cell takes up that radioactive drug and is killed. The radiation from lutetium-177 travels only a short distance outside the target cell, so damage to surrounding normal tissue can be limited.
Lu-PSMA is approved for use in “PSMA-positive” tumors – thus making it a form of precision medicine. This means that the tumor cells have the PSMA protein on their surface, and the Lu-PSMA molecule will be able to bind to them to deliver the radiation.
PCF has invested over $63 million in research on PSMA since inception in 1993. Dr. Neil Bander, currently Professor Emeritus of Urology at Weill Cornell Medicine and Chief Scientific Officer at Convergent Therapeutics, first created an antibody to PSMA that launched the field and helped scientists understand the distribution of PSMA in prostate cancer patients. Read more about PCF’s role in the development of PSMA imaging and therapeutics here.