Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer

Abstract

Prostate-specific membrane antigen (PSMA) is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer (PC), making it an optimal target for the treatment of metastasized PC. Radioligand therapy (RLT) with 177Lu-PSMA-DKFZ-617 (Lu-PSMA) is a targeted therapy for metastatic PC. In this study, we retrospectively analyzed the side effects and the response rate of 24 hormone and/or chemorefractory PC patients with a mean age of 75.2 years (range: 64-82) with distant metastases and progressive disease according to the PSA level, who were treated with Lu-PSMA. Median PSA was 522 ng/ml (range: 17-2360). Forty-six cycles of Lu-PSMA were performed. Of the 24 patients, 22 received two cycles. Eight weeks after the first cycle of Lu-PSMA therapy 79.1% experienced a decline in PSA level. Eight weeks after the second cycle of Lu-PSMA therapy 68.2% experienced a decline in PSA relative to the baseline value. Apart from two cases of grade 3 anemia, there was no relevant hemato- or nephrotoxicity (grade 3 or 4). These results confirmed that Lu-PSMA is a safe treatment option for metastatic PC patients and has a low toxicity profile. A positive response to therapy in terms of decline in PSA occurs in about 70% of patients.

Keywords: 177Lu; PSA; PSMA; prostate cancer; radioligand therapy.

Figure 1. Waterfall plot showing percentage PSA change from baseline at 8 weeks after the first cycle in 23 patients (one patient with multiple liver metastasis died 10 weeks after the first cycle)

79.1 % of patients showed any PSA decline. 41.6 % of patients showed more than 50 % PSA decline.

Figure 2. Waterfall plot showing percentage PSA change from baseline at 8 weeks after the second cycle in 19 patients /22

(3 patients died within 10 weeks after the second cycle).

Figure 3. A 75-year-old patient with diffuse bone and lymph node metastases as well as local recurrence

(left MIP image). History of chemotherapy and therapy with abiretarone, PSA elevation under enzalutamide. The patient underwent PSMA therapy as the last possible option. Continuing PSA decline and partial response in Ga-PSMA PET images after the first (middle MIP image) and second cycles (right MIP image).

Figure 4. Hematotoxicity 2 months after the last cycle according to CTC criteria

Figure 5. Nephrotoxocity 2 months after the last cycle according to CTC criteria

Figure 6. Hepatotoxocity 2 months after the last cycle according to CTC criteria

Figure 7

Ga-PSMA PET images A&B. of a 72-year-old patient with diffuse bone and lymph node metastases (yellow arrows show the enlarged lymph nodes) received two cycles of Lu-PSMA. Ga-PSMA PET images C&D. 2 months after the second cycle show a very good response with reduction in PSMA expression as well as a size reduction of the lymph node metastases in CT B&D.