Reduced-Dose Prostate Cancer Therapies Match Standard Efficacy

Summary: Two reduced-dose radiopharmaceutical therapies for advanced metastatic castrate-resistant prostate cancer are as effective as the standard dose, with similar survival and PSA response rates but better tolerability, according to a study in The Journal of Nuclear Medicine.

Key Takeaways

• Efficacy and Tolerability: Reduced-dose therapies (deescalated 225Ac-PSMA-617 or 177Lu/225Ac-PSMA-617 cocktail) are as effective as the standard dose for advanced metastatic castrate-resistant prostate cancer, with similar overall survival and PSA response rates, but are better tolerated by patients.
• Quality of Life Improvement: Lower doses result in less salivary gland toxicity and dry mouth, improving patients’ quality of life and reducing the likelihood of treatment discontinuation.
• Study Findings: In a retrospective analysis of 233 patients, both reduced-dose regimens showed similar efficacy when adjusted for baseline characteristics, suggesting that patients with late-stage prostate cancer can benefit from these targeted radiopharmaceutical alpha-therapies.

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Two reduced-dose radiopharmaceutical therapies for advanced metastatic castrate-resistant prostate cancer are as effective as the standard dose, according to research in The Journal of Nuclear Medicine. Treatment with deescalated 225Ac-PSMA-617 or a 177Lu/225Ac-PSMA-617 cocktail showed similar median overall survival and PSA response rates as the standard dose and was better tolerated by patients.

Benefits of Lower 225Ac-PSMA Doses for Prostate Cancer

The standard dose for ²²⁵Ac-PSMA targeted radiopharmaceutical alpha-therapy is 100 kBq per kilogram of body weight or an approximation of eight MBq. After multiple treatment cycles of this dose, salivary gland toxicity often increases and patients experience uncomfortable dry mouth. For some patients this impact on their quality of life causes 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 anti-tumor activity,” says Hendrik Rathke, MD, from 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 ²²⁵Ac-PSMA or an ¹⁷⁷Lu/²²⁵Ac-PSMA-617 cocktail therapy.”

Researchers conducted a retrospective analysis of 233 patients who were treated with ²²⁵Ac-PSMA at Heidelberg University Hospital from 2014-2022; 104 received a median of six MBq of ²²⁵Ac-PSMA monotherapy and 129 received an ¹⁷⁷Lu/²²⁵Ac-PSMA-617 cocktail therapy. Baseline characteristics, PSA response, and overall survival were compared with the most appropriate historical controls.

Comparable Efficacy for 225Ac-PSMA and 177Lu/225Ac

Of the patients who received ²²⁵Ac-PSMA monotherapy, 55 patients (53 percent) presented with a best PSA response of at least 50 percent. In the ¹⁷⁷Lu/²²⁵Ac-PSMA-617 cocktail group, a best PSA response of at least 50 percent was observed in 74 patients (57 percent). The median overall survival was nine months in the ²²⁵Ac-PSMA monotherapy and was 15 months in the ¹⁷⁷Lu/²²⁵Ac-PSMA-617 cocktail group. If adjusted for prognostic baseline characteristics, the efficacy of both regimens was not significantly different.

“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,” says Rathke. “This leads to the assumption that patients with late stage prostate cancer can benefit from targeted radiopharmaceutical alpha-therapy.”

Featured image: (A–D) Patient with meningeal, adrenal, pulmonary, lymph nodal, and osseous metastases. (A) Baseline staging per ¹⁸F-PSMA-1007 PET/CT is demonstrated as maximum-intensity projection. (B and C) Two cycles of AcPSMA and LuPSMA cocktail therapy were documented per planar scan of 208-keV γ-line of ¹⁷⁷Lu. (D) PET/CT restaging presents partial remission. (E–H) Patient with adrenal, osseous, lymph nodal, and hepatic metastases. (E) Baseline imaging was done as planar ^99mTc-PSMA scintigraphy. (F and G) AcPSMA monotherapy was documented per planar emission scans using 26% 440-keV and 12% 218-keV γ-coemissions of ²¹³Bi and ²²¹Fr. (H) Restaging per planar ^99mTc-PSMA scintigraphy demonstrates near-total remission.