In a retrospective study (WARMTH Act) reported in The Lancet Oncology, Sathekge et al found that actinium-225–prostate-specific membrane antigen (PSMA) radioligand therapy showed activity in patients with metastatic castration-resistant prostate cancer.
Study Details
The study consisted of 448 consecutive patients treated at seven centers in Australia, India, Germany, and South Africa between January 2016 and May 2023. Patients received one or more cycles of 8 MBq actinium-225–PSMA radioligand therapy (total of 1,174 cycles; median = 2 cycles). Previous treatments in the metastatic setting included docetaxel in 66% of patients, cabazitaxel in 21%, abiraterone in 39%, enzalutamide in 39%, lutetium-177–PSMA radioligand therapy in 32%, and radium-223 dichloride in 4%.
Key Findings
Median overall survival among all patients was 15.5 months (95% confidence interval [CI] = 13.4–18.3 months). Median overall survival was longer in:
- Patients with a prostate-specific antigen decline of ≥ 50% (24.2 months)
- Those without previous exposure to taxane-based chemotherapy (24.2 months), androgen-axis-receptor inhibitors (19.9 months), or lutetium-177–PSMA radioligand therapy (18.8 months)
- Those without liver (17.6 months) or peritoneal (15.7 months) metastases
- Those without anemia at the start of actinium-225–PSMA radioligand therapy (19.4 months).
Median progression-free survival among all patients was 7.9 months (95% CI = 6.8–8.9 months) among all patients. Median progression-free survival was higher among:
- Patients with a prostate-specific antigen decline of ≥ 50% (11.6 months)
- Those without previous exposure to taxane-based chemotherapy (13.9 months), androgen-axis-receptor inhibitors (10.6 months), or lutetium-177–PSMA radioligand therapy (9.3 months)
- Those without liver (8.3 months) or peritoneal (8.0 months) metastases
- Those without anemia at the start of actinium-225–PSMA radioligand therapy (8.8 months)
- Those with Eastern Cooperative Oncology Group performance status of < 2 (8.6 months).
Among 347 patients with available data on treatment-induced xerostomia, 236 (68%) had xerostomia of any grade after the first cycle of treatment. Grade ≥ 3 adverse events among all patients included anemia in 13%, thrombocytopenia in 7%, renal toxicity in 5%, and leukopenia in 4%. No serious adverse events or treatment-related deaths were reported.
The investigators concluded, “Actinium-225 PSMA radioligand therapy shows a substantial antitumor effect in metastatic castration-resistant prostate cancer and represents a viable therapy option in patients treated with previous lines of approved agents. Xerostomia is a common side-effect. Severe bone marrow and renal toxicity are less common adverse events.”
Mike M. Sathekge, MD, of the Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa, is the corresponding author for The Lancet Oncology article.
Disclosure: The investigators reported that here was no external funding for the study. For full disclosures of the study authors, visit thelancet.com.
