Highlights on Lutetium-PSMA from the American Society of Clinical Oncology 2022 Annual Meeting

The American Society of Clinical Oncology (ASCO) Annual Meeting is one of the largest scientific meetings focused on cancer, where physicians, scientists, advocates, and industry partners share the latest developments in research and treatment. 

At the 2022 meeting this summer, there were multiple presentations on ¹⁷⁷ Lutetium-PSMA-617 (Lu-PSMA; PLUVITCO™). This new therapy delivers radiation (the radioisotope ¹⁷⁷Lutetium) directly to prostate cancer cells by binding to the PSMA protein on their surface. It is now FDA-approved in the U.S. Here, we highlight results from two clinical trials of Lu-PSMA:

• Combination treatment of Lu-PSMA and immunotherapy appears promising.
• In comparison with cabazitaxel, better response and fewer side effects were seen with Lu-PSMA. Survival time was similar.

PRINCE Trial: Combination of Lu-PSMA and Immunotherapy Appears Promising

Patients treated with Lu-PSMA eventually progress, and further optimization is needed. Radiation therapies, such as Lu-PSMA, are thought to cause cancer cells to die in a way that alerts the immune system, and thus may synergize with immunotherapy. Immunotherapy has limited effectiveness when used alone in mCRPC. The Phase 1 PRINCE trial evaluated the combination of Lu-PSMA and immunotherapy with pembrolizumab in 37 patients with mCRPC who also had a positive PSMA PET scan.

According to PCF-funded investigator Dr. Shahneen Sandhu, MBBS, of the Peter MacCallum Cancer Centre in Australia, the results were promising. 76% of patients had a PSA response rate (50% or greater decrease in PSA). Seven in 10 (70%) patients with measurable disease on scans had a partial tumor shrinkage. At 12 months, 38% of patients had no evidence of disease progression on scans, and 83% remained alive. 

Common side effects related to treatment were generally mild to moderate, including dry mouth, fatigue, itching, and nausea. More serious immune-related side effects occurred in 27% of patients. Side effects were as expected from data on each treatment alone, and no new side effects were caused by combining the treatments. Measures of well-being, as reported by patients, remained stable.

What this could mean for patients: The combination of Lu-PSMA and immunotherapy with pembrolizumab has potential to benefit patients with mCRPC, and requires further study in larger, randomized, longer-term clinical trials.

New Results from the TheraP Trial Comparing Lutetium-PSMA vs. Cabazitaxel

The randomized TheraP trial is comparing the new radiopharmaceutical¹⁷⁷ Lutetium-PSMA-617 (Lu-PSMA) to the chemotherapy drug cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). Study leader and PCF-funded investigator Prof. Michael Hofman, MBBS, of the Peter MacCallum Cancer Centre presented results after 3 years of follow up. Patients treated with Lu-PSMA had better response rates, fewer side effects, and similar survival vs. cabazitaxel.

The 200 patients in the trial had mCRPC and had progressed on docetaxel, and over 90% had been treated with enzalutamide or abiraterone. They also had PSMA PET imaging showing high levels of the PSMA protein on prostate cancer cells. The initial results strongly favored Lu-PSMA.
 

• 66% of participants who received Lu-PSMA experienced a PSA response (defined as a decrease in PSA by 50% or more), compared to 37% of participants treated with cabazitaxel.
• More patients treated with Lu-PSMA had a response as seen on imaging: 49% vs. 24% in the cabazitaxel group.
• Fewer patients treated with Lu-PSMA had severe side effects (33% vs. 53%).

After 3 years of follow-up, there was no significant difference in average overall survival: 19.1 months with Lu-PSMA vs. 19.6 months with cabazitaxel. During this longer follow-up period, no significant new side effects were seen with Lu-PSMA. Hofman noted that one limitation of the trial was that some patients treated with cabazitaxel withdrew from the trial and opted to receive treatment with Lu-PSMA. This may have affected patients’ survival and, ultimately, the trial results.

What This Means for Patients

Based on the results of this trial, Lu-PSMA may be a suitable choice for patients with mCRPC who have progressed on docetaxel and have a positive PSMA PET scan. This is based on higher response rates, lower rates of side effects, and better quality of life with Lu-PSMA vs. cabazitaxel. However, if a patient cannot access Lu-PSMA, cabazitaxel may be an option, given that it is a known, life-prolonging therapy, and the two treatments have similar survival outcomes. If you have mCRPC, talk to your doctor about your treatment options.

Progress in Prostate Cancer Research provides hope for finding a cure and the discovery of new treatments to minimize the impact of a man’s prostate cancer and maximize his quality of life. This regular ZEROHour supplement includes some of the latest research from the Prostate Cancer Foundation.

Written by Prostate Cancer Foundation. PCF is the world’s leading philanthropic organization dedicated to funding life-saving prostate cancer research. Since it was founded in 1993, PCF has funded more than 2,200 research projects at 245 leading cancer centers in 28 countries around the world. For more information, go to www.pcf.org or call 1-800-757-CURE.