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

BACKGROUND: Promising therapeutic results of the prostate-specific membrane antigen (PSMA) ligand have been shown when labelling with lutetium-177 (Lu-177). We performed a systematic review and meta-analysis to assess the therapeutic response of Lu-177-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 177 Lu-PSMA, analysing two measures: 'any PSA decline' and '450% decline' from baseline. A random-effects meta-analysis was used to calculate the pooled proportion across studies. The I-2 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 (Lu-177-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 I-2 statistic was 39.1% (P = 0.11) suggesting minor heterogeneity between results. The pooled proportion of patients with 450% PSA decline was 37% (95% CI: 22-52). The I-2 statistic was 91.0% (P<.001) suggesting substantial heterogeneity between results. On subgroup analysis, a higher proportion of patients in the Lu-177-DKZ/I&T subgroup had a PSA decline450%, however, it can be seen that the Lu-177-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.