Lu-PSMA-617 in combination with third-line therapy for castration-resistant prostate cancer: A systemic review and meta-analysis

e17051 Background: Prostate cancer is the second most common cancer and the sixth leading cause of cancer death among men worldwide. Lu-177 viptriplet, also known as lutetium-177-PSMA-617, is a highly targeted form of radioligand therapy that aims to shrink prostate cancer tumors and slow their progression. It is also recommended as a treatment option by the American Society of Clinical Oncology (ASCO) for patients with prostate-specific membrane antigen (PSMA) positive PET/CT-positive castration resistant prostate cancer (CRPC) who have progressed on at least one prior line of androgen receptor pathway inhibitors (ARPI) and at least one prior line of chemotherapy. However, the evidence on its effectiveness with third-line chemotherapy is scarce. We aim to evaluate the efficacy of Luma-PSMA plus third-line chemotherapy in CRPC. Methods: We conducted a comprehensive literature search in PubMed, PMC, Scopus, and Embase using relevant keywords to identify articles related to Luma-PSMA and third line chemotherapy for prostate cancer from inception to Jan 30, 2023. Three independent reviewers screened the articles for eligibility and extracted data on outcomes such as overall survival (OS), PSA decline > 50%, and partial remission. We used Raveman 5 software to perform a statistical analysis and calculated the odds ratio with a 95% confidence interval for each outcome. Results: A total of 11 studies were included in our analysis with 787 patients. Pooled analysis of studies demonstrated an overall survival after Lu-PSMA-617 therapy plus third line chemotherapy as compared to standalone chemotherapy in castration resistant prostate cancer to be 13.15 months (95% CI = 10.66 – 15.65, P = < 0.001, I 2 = 69.93%). Pooled prevalence of prostate specific antigen (PSA) decline > 50% was determined to be 49.5% (95% CI = 44.2 – 54.7, P = 0.162 I 2 = 33.27%) and partial remission was observed in 39.7% patients (95% CI = 28.5 – 50.9, P = 0.952 I 2 = 0%). Conclusions: Our meta-analysis suggests that Lu-PSMA-617 therapy plus third-line chemotherapy may improve overall survival and PSA response in patients with CRPC compared to chemotherapy alone. However, the quality of evidence is limited by heterogeneity and risk of bias. More high-quality randomized trials are needed to confirm the efficacy and safety of this combination therapy. [Table: see text]