Radioactive Lutetium-177 Compound Shows Promise As Therapy For Metastatic, Hormone-Resistant Prostate Cancer.

Treatment with the radioactive molecule lutetium-177-PSMA-617 (LuPSMA), which binds to the prostate-specific membrane antigen, is a potential therapeutic strategy for patients with metastatic castration (hormone)-resistant prostate cancer (CRPC), results from a Phase II pilot study suggest.

Prostate-specific membrane antigen (PSMA) is found at high levels in prostate cancers, particularly in patients with hormone-resistant disease — a form of cancer that no longer responds to hormone therapy and continues to progress. More research is assessing the potential of using agents that target this protein to deliver radioactive compounds directly into cancer cells. The LuPSMA molecule is composed of an anti-PSMA antibody bound to the radioactive compound Lutetium-177. Its safety and efficacy are being assessed in a pilot Phase 1/2 study by researchers at the Peter MacCallum Cancer Centre, Melbourne, Australia.

The trial enrolled 50 metastatic CRPC patients whose tumors were positive for the PSMA factor. Their cancer had progressed after standard treatments, including hormone therapy and chemotherapy, and they were offered four doses of LuPSMA, each given six weeks apart. Participants had rapidly progressing disease, taking 2.6 months to double their PSA levels — a marker of prostate cancer. Most patients had received the chemotherapies docetaxel (Taxotere; 84%) and  cabazitaxel (Jevtana; 48%). Hormone therapy with Zytiga (abiraterone), Xtandi (enzalutamide) or a combination of both had been given to 90% of patients.

The study’s primary goals were to measure the number of patients whose PSA levels dropped and the treatment’s toxicity. Additional objectives included imaging responses, time patients lived without disease worsening, overall survival, and quality of life scores.

Investigators reported a reduction in PSA levels by at least 50% in 64% of patients, including 44% who experienced a reduction of at least 80%. Among the 27 patients with measurable disease at the study’s start, 56% experienced a partial or complete tumor reduction. The median time patients lived without disease worsening — measured through a rise in PSA levels — was 6.9 months. Their median overall survival was 13.3 months. A total of 14 patients received additional LuPSMA doses after their disease progressed. In nine of these patients (64%), PSA levels reduced by at least 50%. The most common side effects were dry mouth, nausea, and fatigue. Serious side effects were rare and included abnormally low levels of platelets and anemia, both detected in 10% of cases.

Overall, these early findings confirm the “high response rates and low toxicity with LuPSMA in men who had progressed after standard therapies,” even “in patients who subsequently progressed and were administered further LuPSMA,” the researchers wrote. “These results have provided the basis for randomised controlled trials currently underway,”

These findings were shared in a poster presented at the  2019 Genitourinary Cancers Symposium, Feb. 14–16 in San Francisco.

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