Efficacy and Safety of Prostate-Specific Membrane Antigen-Targeted Endoradiotherapy in Metastatic Castration-Resistant Prostate Cancer

30 Jul, 21

Introduction

Prostate-specific membrane antigen (PSMA)-targeted endoradiotherapy/radioligand therapy (PRLT) with small-molecule, urea-based agents labeled with the ?-particle–emitting radionuclide lutetium-177 (¹⁷⁷Lu) offers promise in the treatment of castration-resistant prostate cancer (CRPC). The 2 most common 177Lu-labeled PSMA-targeted ligands are 177Lu-PSMA -617 and 177Lu-PSMA-I&T. The outcomes of PRLT on CRPC has been analyzed. However, there are no comprehensive studies on the toxicities and severities of toxicities associated with this therapy.

Aim

This systematic review and meta-analysis assessed the efficacy and toxicity of Lu-labeled PSMA-targeted PRLT in patients with CRPC.

Method

Study Design

Systematic review and meta-analysis.

Evidence Acquisition

PubMed/Medline databases were extensively searched to identify 250 studies, out of which 24 studies with 1192 patients were included in the analysis.
Proportions of patients with ≥50% serum prostate-specific antigen (PSA) decrease, any PSA decrease, and any PSA increase were extracted.
Toxicities were extracted based on Common Terminology Criteria for Adverse Events (CTCAE) grading system
Toxicities were classified into any-grade CTCAE toxicity and grade 3 or 4 CTCAE toxicities.
Overall survival and progression-free survival were assessed.
A meta-analysis of single proportions was conducted for the proportion of patients demonstrating a PSA decrease of >50%
The efficacy and toxicity outcomes of ¹⁷⁷Lu-PSMA were compared with ¹⁷⁷Lu-PSMA-I&T.

Endpoints

Proportion of patients demonstrating >50% PSA reduction
OS based on hazard ratios (HRs) of OS according to any PSA decrease and a PSA decline of >50%
PFS based on HRs according to PSA decline of >50%
Proportion of patients with any-grade toxicity and grade 3 or 4 toxicities

Results

Out of a total of 24 studies, 20 included data on ¹⁷⁷Lu-PSMA-617, 3 used ¹⁷⁷Lu-PSMA-I&T, and one study reported aggregated data for ¹⁷⁷Lu-PSMA-617 and ¹⁷⁷Lu-PSMA-I&T.
The estimated proportion of ¹⁷⁷Lu-PSMA-617–treated patients and ¹⁷⁷Lu-PSMA-I&T-treated patients who demonstrated a serum PSA decline of ≥50% with at least an 8-wk interval between therapy and PSA measurement was 0.44 and 0.36 respectively.
The aggregate results for men treated with more than one cycle of any kind of PRLT showed an estimated proportion of 0.46 for PSA response ≥50%.
There were no significant differences in the toxicities between the 2 groups.
Overall, grade 3 and 4 toxicities were uncommon, with estimated proportions from 0.01 for nausea, fatigue, diarrhea, and elevated aspartate transaminase up to 0.08 for anemia.
Anemia was the most common complication with regards to CTCAE grade 3 or 4 toxicities associated with both the agents.
The pooled HR for OS of any PSA decline was 0.29 and for patients with >50% PSA reduction was 0.67.
The pooled HR for PFS of >50% PSA reduction was 0.53.

Conclusion

Prostate-specific membrane antigen (PSMA)-targeted endoradiotherapy/radioligand therapy (PRLT) with small-molecule, urea-based agents labeled with the ?-particle–emitting radionuclide lutetium-177 (¹⁷⁷Lu) is highly effective and safe in the treatment of castration-resistant prostate cancer (CRPC).
PRLT was associated with relatively high number of prostate-specific antigen (PSA) responders coupled with low rate of severe toxicity.
This systematic review and meta-analysis might be valuable to the clinicians who can balance the risks and benefits of this novel therapy in CRPC.

Eur Urol. 2021 Jul;80(1):82-94. Doi: 10.1016/j.eururo.2021.03.004.