by Dr. C.H. Weaver M.D. 12/2018
177Lu-PSMA-617 is a member of a new class of drugs that deliver radiation directly to tumor cells to obliterate them. These targeted radiation treatments consist of a radioactive isotope attached to a molecule that specifically targets tumor cells. In this case, the radioactive isotope is 177-lutetium (177Lu), an unstable form of the element lutetium, which shoots off high-energy beta particles when it decays. Beta particles kill cells by bombarding and breaking their DNA. PSMA-617 is a small molecule that specifically binds to PSMA (prostate specific membrane antigen), a protein that is present at high levels on 90-95% of prostate cancers, including most metastatic castration-resistant prostate cancers (mCRPC). PSMA is absent or present at very low levels on most other tissues in the body, a property that is important in limiting side effects of targeted therapies.
This new type of therapy is being tested for prostate cancer in many different forms (different isotopes attached to different PSMA-targeting molecules), and has received a significant amount of interest from the medical community due to exciting but anecdotal case reports. Clinical trials are needed to prove safety and efficacy, as well as to figure out the best way to use these treatments in patients.
A prospective, single-arm phase 2 clinical trial to test 177Lu-PSMA-617 in 30 men with mCRPC whose tumors express PSMA was performed. All but two of the men had previously received and progressed after standard treatments. The men were treated with between one to four cycles of 177Lu-PSMA-617. Following treatment their PSA levels dropped by over 50% in 17 of the 30 (57%) patients treated, and by over 30% in 21 (70%) patients. Tumors stopped growing or shrank in many patients, including complete or partial tumor shrinkage in 14 of 17 (82%) patients who had metastatic tumors in lymph nodes and other non-bone sites on CT scans.
Overall the treatment was well tolerated and the most common side effects included low-grade dry mouth (87% of patients) and low to high grade decreases in white blood cell (37% grade 1-2; 37% grade 3) and platelet counts (27% grade 1-2; 10% grade 3), anemia (13% grade 1-2; 13% grade 3), and pain (17% grade 1-2; 3% grade 3). Some patients also experienced low-grade dry eyes (17%), fatigue (50%), nausea (50%), vomiting (33%), anorexia (23%), and weight loss (10%).
Despite side effects, patients experienced clinically meaningful pain alleviation and improvements in overall quality of life. A randomized phase 3 clinical trial comparing 177Lu-PSMA-617 plus best supportive/best standard of care versus best supportive/best standard of care alone was initiated to confirm the benefit of 177Lu-PSMA-617 and is ongoing at this time.