Assessment of the therapeutic efficacy of [177Lu]Lu-PSMA-X compared to taxane chemotherapy in taxane-chemo-naïve patients with metastatic castration-resistant prostate cancer: A systematic review and meta-analysis

• Published in: European journal of nuclear medicine and molecular imaging 2024-10, Vol.52 (3), p.936-954
• Main Authors: Almeida, Ludmila Santiago, García Megías, Irene, Etchebehere, Elba Cristina Sá Camargo, Calapaquí Terán, Adriana K., Herrmann, Ken, Giammarile, Francesco, Treglia, Giorgio, Delgado Bolton, Roberto C.
• Format: Article
• Language: English
• Subjects: Androgen receptors; Antigens; Cancer therapies; Cardiology; Castration; Chemical compounds; Chemotherapy; Effectiveness; Heterogeneity; Imaging; Inhibitors; Lutetium isotopes; Medicine; Medicine & Public Health; Meta-analysis; Metastases; Metastasis; Nuclear Medicine; Oncology; Original Article; Orthopedics; Pharmacology; Prostate cancer; Radiology; Response rates; Survival; Systematic review; Taxanes
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-024-06932-2

Introduction and aim Radioligand therapy (RLT) with 177 Lu-labelled prostate specific membrane antigen ([ 177 Lu]Lu-PSMA-X, referring with “PSMA-X” to a generic PSMA chemical compound) inhibitors has emerged as a viable treatment option in metastatic castration resistant prostate cancer patients having previously progressed on taxane and androgen receptor inhibitors. The aim of this study was to perform a systematic review and meta-analysis to assess the therapeutic efficacy of [ 177 Lu]Lu-PSMA-X compared to taxane chemotherapy in taxane-chemo-naïve patients with metastatic castration-resistant prostate cancer. Materials and methods Searches in several bibliographic databases were made using relevant key words, and articles published up to March 2024 were included. The endpoints included prostate specific antigen (PSA) response rate (RR), progression-free survival, and overall survival. Individual patient data were pooled when feasible. PSA50 was defined as the median proportion of patients achieving at least a 50% decline in serum PSA from baseline. A meta-analysis of the PSA50 response rate (proportion meta-analysis) was performed, generating pooled estimates and 95% confidence intervals (95% CI). Results From the initially selected 8,414 studies published between 2019 and 2023, 24 were included in the [ 177 Lu]Lu-PSMA-X treated group and 17 in the taxane treated group. Our findings show that [ 177 Lu]Lu-PSMA-X RLT yielded comparable PSA50 responses in taxane-naïve patients versus those receiving taxane chemotherapy, despite considerable study heterogeneity. Notably, the taxane-naïve group had more extensive pretreatment. Conclusions This meta-analysis combines the largest cohorts of taxane-naïve mCRPC patients treated with [ 177 Lu]Lu-PSMA-X RLT and taxane-treated mCRPC. It underscores similar PSA50 response rates in both groups, suggesting a potential role for [ 177 Lu]Lu-PSMA-X RLT in taxane-naïve patients who cannot or choose not to undergo chemotherapy.