177Lu-PSMA Radioligand Therapy Is Favorable as Third-Line Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Finn E Von Eyben,Manuela Andrea Hoffmann,Giandomenico Roviello,Kalevi Kairemo,Giovanni Paganelli,Irene Virgolini,Channing Paller

doi:10.3390/biomedicines9081042

Abstract

In this systematic review and network meta-analysis (NMA), we aimed to assess the benefits and harms of third-line (L3) treatments in randomized controlled trials (RCTs) of patients with metastatic castration-resistant prostate cancer (mCRPC). Two reviewers searched for publications from 1 January 2006 to 30 June 2021. The review analyzed seven RCTs that included 3958 patients and eight treatments. Treatment with prostate-specific membrane antigen (PSMA)-based radioligand therapy (PRLT) resulted in a 1.3-times-higher rate of median PSA decline ≥50% than treatment with abiraterone, enzalutamide, mitoxantrone, or cabazitaxel (p = 0.00001). The likelihood was 97.6% for PRLT to bring about the best PSA response, out of the examined treatments. PRLT resulted in a 1.1-times-higher six-month rate of median radiographic progression-free survival. Treatment with PRLT in the VISION trial resulted in 1.05-times-higher twelve-month median overall survival than L3 treatment with cabazitaxel in other RCTs. PRLT more often resulted in severe thrombocytopenia and less often in severe leukopenia than did cabazitaxel. In conclusion, for patients with mCRPC, L3 treatment with PRLT is highly effective and safe.

Highlights

For men in Western societies, prostate cancer is the second leading cause of cancer death [1]
Most deaths from prostate cancer are due to advanced metastatic castrationresistant prostate cancer
We evaluated the best PSA response and radiological progression-free survival, as recommended by the Prostate Cancer Clinical Trial Working Group 3 (PCWG3) [21]

Summary

Introduction

For men in Western societies, prostate cancer is the second leading cause of cancer death [1]. Most deaths from prostate cancer are due to advanced metastatic castrationresistant prostate cancer (mCRPC). Several drugs prolong life for patients with mCRPC [2]. In 2018, guidelines from the European Association of Urology (EAU) recommended that, as a first-line (L1) treatment, patients with mCRPC be treated either with a combination of Biomedicines 2021, 9, 1042. Biomedicines 2021, 9, 1042 androgen deprivation therapy (ADT) and abiraterone or with a combination of ADT and docetaxel [3]. Established drugs prolong median overall survival by many months [4,5]. In the European Union each year, more than 20,000 patients may be candidates for L3 treatment

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