[177Lu]Lu-PSMA-Radioligand Therapy Efficacy Outcomes in Taxane-Naïve Versus Taxane-Treated Patients with Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Metaanalysis.

Radioligand therapy (RLT) with ¹⁷⁷Lu-prostate-specific membrane antigen (PSMA) inhibitors ([¹⁷⁷Lu]Lu-PSMA) is currently approved for patients with metastatic castration-resistant prostate cancer (mCRPC) after progression with at least 1 taxane and 1 androgen-receptor-pathway inhibitor. However, the impact of prior chemotherapy on [¹⁷⁷Lu]Lu-PSMA-RLT outcomes is debatable, with various studies showing inconsistent results. This study was conducted to precisely evaluate the impact of prior taxane chemotherapy on response and survival outcomes in mCRPC patients after [¹⁷⁷Lu]Lu-PSMA-RLT. Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches in PubMed, Scopus, and Embase were made using relevant key words, and articles up to December 2022 were included. The endpoints included prostate-specific antigen (PSA) response rate (RR), progression-free survival, and overall survival (OS). Individual patient data were pooled when feasible. Univariate odds ratios (ORs) and hazard ratios (HRs) were extracted from the individual articles, and pooled estimates and 95% CIs were generated using metaanalysis. Results: Thirteen articles comprising 2,068 patients were included. In 6 articles (553 patients), taxane-naïve patients had significantly better odds of biochemical response after [¹⁷⁷Lu]Lu-PSMA-RLT (pooled OR, 1.82; 95% CI, 1.21-2.71). Individual patient data metaanalysis for PSA RRs in 3 articles revealed a significantly higher PSA RR in the taxane-naïve versus taxane-treated patients (57.1% vs. 39.5%; difference, 17.6%; 95% CI, 5.6%-28.9%). Further, taxane-naïve status was also a predictor of significantly better progression-free survival (5 articles; 1,027 patients; pooled HR, 0.60; 95% CI, 0.51-0.69) and OS (8 articles; 1,594 patients; pooled HR, 0.54; 95% CI, 0.43-0.68) after [¹⁷⁷Lu]Lu-PSMA-RLT. There was no evidence of publication bias. Conclusion: mCRPC patients with no prior taxanes had significantly better outcomes after [¹⁷⁷Lu]Lu-PSMA-RLT than did taxane-treated patients. Further trials evaluating [¹⁷⁷Lu]Lu-PSMA-RLT in the taxane-naïve setting are now required.