Radioligand therapy using [ 177 Lu]Lu-PSMA-617 in mCRPC: a pre-VISION single-center analysis.

Background: Radioligand therapy with [ ¹⁷⁷ Lu]Lu-PSMA-617 is efficacious for the treatment of patients with metastasized castration-resistant prostate cancer (mCRPC). Various studies have evaluated the efficacy and safety of [ ¹⁷⁷ Lu]Lu-PSMA-617 using a dose of 6.0 GBq and an 8-week therapy interval. However, the first prospective phase III trial (VISION) plans to use an elevated cumulative dose by applying 7.5 GBq in a 6-week interval. The aim of the present study was to compare safety and efficacy of the two aforementioned [ ¹⁷⁷ Lu]Lu-PSMA-617 therapy regimes (7.5 GBq every 6 weeks vs. 6.0 GBq every 8 weeks).
Methods: A total number of 78 consecutive patients with mCRPC and a history of first-line chemotherapy were included in this retrospective analysis. The outcome of patients treated with 6.0 GBq [ ¹⁷⁷ Lu]Lu-PSMA-617 per cycle (n = 37) were compared with those treated with 7.5 GBq (n = 41) per cycle. The median therapy intervals were 8.4 weeks (6.0 GBq group) vs. 6.5 (7.5 GBq group). PSA response, PSA progression-free survival (PSA-PFS), overall survival, and adverse events were evaluated and compared between both groups. Chi-squared test, Kaplan Meier estimates, Cox regression, and log-rank test were used. The highest decline from pretherapeutic PSA levels was measured as percentage (best PSA response) and compared between groups by Wilcoxon test.
Results: There was no significant difference comparing the rate of > 50% PSA decline or best PSA response between the 6.0 GBq and 7.5 GBq group (35% vs. 54%, p = 0.065; and - 40.2% vs. - 57.8%, p = 0.329). The median estimated survival and PSA-PFS did not significantly differ between the 6.0 GBq and 7.5 GBq groups as well (11.3 vs. 12.7 months, p = 0.384; and 9.5 vs. 12.3 months, p = 0.258). There was no significant difference regarding the change of kidney, liver, and blood cell parameters under therapy between the treatment groups.
Conclusion: Higher cumulated doses of [ ¹⁷⁷ Lu]Lu-PSMA-617 were well tolerated and caused no significantly increased rate of adverse reactions. Moreover, 7.5 GBq of [ ¹⁷⁷ Lu]Lu-PSMA-617 every 6 weeks causes slightly higher, though not statistically significant, response rates and seems therefore to be the preferable treatment regime. However, future studies are needed to elucidate the dose-related efficacy of [ ¹⁷⁷ Lu]Lu-PSMA-617 as a way to personalized medicine.