Lutetium-177 PSMA radioligand therapy in taxan-naive first- and second-line metastatic castration resistant prostate cancer after first-line ARPI therapy.

Purpose: Lutetium-177 Prostate-specific membrane antigen (Lu-PSMA) radioligand therapy is EMA-approved for metastatic castration resistant prostate cancer (mCRPC) after androgen receptor pathway inhibition (ARPI) and taxan-based chemotherapy. However, its effect in taxan-naïve patients is under current investigation.

Methods: We relied on the FRAMCAP database to elaborate Lu-PSMA therapy outcomes of progression-free (PFS) and overall (OS) in taxan-naïve mCRPC patients after previous ARPI treatment. Comparison was made against current standard of care with ARPI or docetaxel, irrespective of the previous used staging modality.

Results: Of 269 patients, 11% received Lu-PSMA in first/second-line mCRPC vs. 57% ARPI vs. 33% docetaxel. Mostly no significant baseline differences between Lu-PSMA and ARPI patients were observed, while Lu-PSMA patients were significantly older, received less systematic treatments and ECOG1-2 proportions were higher, relative to docetaxel patients. In PFS (13.3 vs. 8.2 months, hazard ratio [HR]: 0.70, p = 0.16) and OS analyses (68.9 vs. 39.1 months, HR: 0.64, p = 0.2), Lu-PSMA was numerically more favorable than ARPI. In additional multivariable Cox regression models, Lu-PSMA was significant better regarding PFS and OS, relative to ARPI (both p < 0.05). Compared to docetaxel, also significant better PFS (13.3 vs. 8.1 months, HR: 0.46) and OS (68.9 vs. 27.3 months, HR: 0.34, both p < 0.01) was observed for Lu-PSMA treatment. The OS advantage was also observed after multivariable adjustment (p < 0.01).

Conclusion: This retrospective single-center study including a substantial proportion of patients with treatment preference for Lu-PSMA suggests that Lu-PSMA therapy provides significantly more favorable PFS and OS outcomes in taxan-naïve mCRPC patients after previous ARPI treatment, relative to ARPI or docetaxel treatment and may be considered as an early mCRPC treatment option.