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

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.

Comparison of [18F]PSMA-1007 with [68Ga]Ga-PSMA-11 PET/CT in Restaging of Prostate Cancer Patients with PSA Relapse

“…The differentiation between 68 Ga-PSMA positive and negative scans was not statistically significant (mean PSA: 8.39 ± 23 vs. 4.22 ± 5.99 ng/mL, median PSA: 2.71 vs. 1.40 ng/mL, n.s.). The detection efficacy in the patient group Ga-RP was 75% (12) for PSA levels of 0.2 to <0.5 ng/mL, 86.7% (13), 76.9% (10), 94.4% (17), and 88.9% (24) for PSA levels of 0.5 to <1, 1 to < 2, 2 to < 5, and ≥5 ng/mL, respectively (p = 0.108) (Table 6). All of the 28 BCR patients in the F-RT patient group showed a positive 18 F-PSMA scan (100%) (mean PSA 9.10 ± 10.16 ng/mL) with 15 patients with PSA levels of 2 to <5 ng/mL and 13 patients with PSA values of ≥5 ng/mL, respectively.…”

“…Thus, PSMA provides an optimal target for diagnosis and therapy of PC lesions. Several PSMA ligands for labeling with 68 Gallium ( 68 Ga) and 18 Fluor ( 18 F) have been developed in recent years and nuclear medicine physicians continue to investigate imaging with [ 68 Ga]Ga-PSMA-11 PET/CT ( 68 Ga-PSMA) and with [ 18 F]PSMA-1007 PET/CT ( 18 F-PSMA) [9][10][11][12]. Compared to 68 Garadiolabeled tracers, the 18 F radionuclides offer advantages in terms of physical properties such as longer half-life and lower positron range with a higher image resolution [9].…”

Efficacy and Safety of 225Ac-PSMA-617-Targeted Alpha Therapy in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

“…In a meta-analysis of randomized controlled trials in patients with mCRPC, the benefits and harms of eight third-line (L3) treatments for prostate cancer were evaluated. Compared with treatment with abiraterone, enzalutamide, mitoxantrone or cabazitaxel, PSMA PRLT resulted in a higher rate of PSA decline and a 1.1-fold increase in PFS (30). Although it was a preliminary study, it had shown the great potential of targeted radionuclide therapy.…”

PSMA targeting in metastatic castration-resistant prostate cancer: where are we and where are we going?

“…Von Eyben et al conducted two extensive reviews of the literature to compare, in the absence of phase III study data available at that time, the efficacy of PRLT to third-line systemic treatment of metastatic castration-resistant prostate cancer (mCRPC). 17,18 A PSA50 is observed in 44% of patients with PRLT compared to 22% for third-line systemic therapy ( p = 0.0002, t test). In addition, the objective response rate was greater for PRLT compared to third-line systemic therapy (28% versus 16%, p = 0.004); as was median survival, albeit not significantly so (14 months versus 12 months, p = 0.32).…”