Long-term outcome of 177Lu-PSMA-617 radioligand therapy in heavily pre-treated metastatic castration-resistant prostate cancer patients

Abstract

Objective Investigators have extensively explored the short-term safety and efficacy data on 177Lu-PSMA-617 radioligand therapy (RLT) in mCRPC patients. However, scarce literature is reported on the long-term outcome of these patients. The current goal of this study is focused on the long-term outcome of mCRPC patients treated with 177Lu-PSMA-617 RLT. Methods Among 135 patients, 121 mCRPC patients fulfilled the eligibility criteria and were included in the final analysis. Patients received a median of 3 cycles of 177Lu-PSMA-617 RLT at 6 to 12-week intervals. Primary endpoint included overall survival (OS) and secondary endpoints involved progression-free survival (PFS), predictive factors of OS and PFS, PSA response rate, molecular response, clinical response, and toxicity assessment. Results The median administered cumulative activity was 20 GBq (3.7–37 GBq). The median follow-up duration was 36 months (6–72 months). The estimated median PFS and OS were 12 months (mo) (95% CI: 10.3–13 mo) and 16 mo (95% CI: 13–17 mo), respectively. Any PSA decline and PSA decline >50% was achieved in 73% and 61% of the patients, respectively. Multivariate analysis revealed only failure to achieve >50% PSA decline as a significant factor associated with a poor PFS. Prognostic factors associated with reduced OS included, failure to experience >50% PSA decline, heavily pre-treated patient cohort who received >2 lines of prior treatment options, and patient sub-group treated with ≥2 lines of chemotherapy. Patients re-treated with additional treatment options after attaining 177Lu-PSMA refractory disease showed a remarkably prolonged OS. A significant clinical benefit was achieved post 177Lu-PSMA-617 RLT. The most common toxicities observed were fatigue (34.7%), followed by nausea (33%), and dry mouth (24.7%). Conclusion The current study supports the short-term safety and efficacy results of high response rates, prolonged PFS and OS, improved quality of life, and low treatment-related toxicities in patients treated with 177Lu-PSMA-617 radioligand therapy.