Lutetium-177-labelled anti-prostate-specific membrane antigen antibody and ligands for the treatment of metastatic castrate-resistant prostate cancer: a systematic review and meta-analysis

Abstract

Background: Promising therapeutic results of the prostate-specific membrane antigen (PSMA) ligand have been shown when labelling with lutetium-177 (¹⁷⁷Lu). We performed a systematic review and meta-analysis to assess the therapeutic response of ¹⁷⁷Lu-PSMA in the treatment of metastatic castration-resistant prostate cancer (mCRPC).

Methods: A systematic review was conducted using electronic databases up to December 2016. Two reviewers independently extracted data and assessed methodological quality. The main outcome of interest was antitumour biochemical response of ¹⁷⁷Lu-PSMA, analysing two measures: 'any PSA decline' and '>50% decline' from baseline. A random-effects meta-analysis was used to calculate the pooled proportion across studies. The I² statistic was calculated in each case to investigate the extent of heterogeneity across the studies. A sensitivity analysis was conducted removing two studies, which were presented as abstracts and proportions were summarised by chemical type (¹⁷⁷Lu-J591/DKZ/I&T). All analyses were conducted using Stata v14.

Results: A total of 10 studies were included in the analysis giving a total sample size of 369, 220 (of 334 analysable) experienced any PSA decline. The pooled proportion of patients with any PSA decline was 68% (95% confidence interval (CI): 61-74). The I² statistic was 39.1% (P=0.11) suggesting minor heterogeneity between results. The pooled proportion of patients with >50% PSA decline was 37% (95% CI: 22-52). The I² statistic was 91.0% (P<0.001) suggesting substantial heterogeneity between results. On subgroup analysis, a higher proportion of patients in the ¹⁷⁷Lu-DKZ/I&T subgroup had a PSA decline >50%, however, it can be seen that the ¹⁷⁷Lu-DKZ/I&T subgroup had a substantial amount of heterogeneity across studies.

Conclusions: This review suggests promising early results for the treatment of mCRPC, especially from patients treated with the more recently developed radioligands. Overall, our meta-analysis showed that approximately two-thirds of patients had a biochemical response. Randomised-controlled trials would be necessary to verify its effectiveness against current systemic therapies and create an ideal treatment protocol.