Treatment with de-escalated actinium (Ac)-225–prostate-specific membrane antigen (PSMA)-617 or a combination of lutetium (Lu)-177/Ac-225–PSMA-617 resulted in similar median overall survival and prostate-specific antigen (PSA) response rates and better tolerance among patients with advanced-stage metastatic castration-resistant prostate cancer compared with the standard Ac-225–PSMA-617 dose, according to a recent study published by Rathke et al in The Journal of Nuclear Medicine.
Background
The standard dose for Ac-225–PSMA-targeted radiopharmaceutical alpha-therapy is 100 kBq/kg of body weight or approximately 8 MBq. However, following multiple treatment cycles of this dose, salivary gland toxicity often increases and patients experience uncomfortable dry mouth. For some patients, the impact on their quality of life may cause them to discontinue treatment.
“Preliminary data from other studies has shown that reduced doses of PSMA treatment result in lower rates of dry mouth while still maintaining promising antitumor activity,” highlighted lead study author Hendrik Rathke, MD, of the Department of Nuclear Medicine at Heidelberg University Hospital in Germany. “In our study we aimed to determine the tolerability, PSA response rate, and overall survival observed in patients who received a regimen of less than 100 kBq of Ac-225–PSMA or a Lu-177/Ac-225–PSMA-617 cocktail therapy,” he added.
Study Methods and Results
In the recent study, researchers conducted a retrospective analysis of 233 patients who were treated with Ac-225–PSMA-617 between 2014 and 2022—104 of whom received a median of 6 MBq of Ac-225–PSMA-617 monotherapy and 129 of whom received a combination of Lu-177/Ac-225–PSMA-617 therapy. They compared the patients’ baseline characteristics, PSA response, and overall survival with the most appropriate historical controls.
The researchers discovered that 53% (n = 55) of the patients who received Ac-225–PSMA-617 monotherapy presented with a best PSA response of at least 50% vs 57% (n = 74) of the patients who received the Lu-177/Ac-225–PSMA-617 combination therapy. The median overall survival was 9 months in the Ac-225–PSMA monotherapy group compared with 15 months in the Lu-177/Ac-225–PSMA-617 combination therapy group. If adjusted for prognostic baseline characteristics, there were no statistically significant differences in the efficacy of both regimens.
Conclusions
“The baseline prognostic characteristics of patients in this study are worse than patients who were recruited to the VISION clinical trial, yet the median overall survival and PSA response rates are equivalent,” underscored Dr. Rathke. “This leads to the assumption that patients with late-stage prostate cancer can benefit from targeted radiopharmaceutical alpha-therapy,” he concluded.
Disclosure: For full disclosures of the study authors, visit jnm.snmjournals.org.
