Radium-223 對 mCRPC 患者總存活期的療效評估：一項統合分析

張雁翔¹、羅浩倫²、陳力瑜³、林湘凌³、黃雅庭³

高雄長庚紀念醫院 核子醫學科¹ ;

高雄長庚紀念醫院 泌尿科² ;

普瑞默生物科技股份有限公司³

The evaluation in the efficacy of Radium-223 for overall survival among patients with mCRPC: A meta-analysis

Yen-Hsiang Chang¹, Hao Lun Luo², Li Yu Chen³, Shiang ling Lin³, Ya Ting Huang³

Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan¹;

Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Taiwan²;

Primo Biotechnology Co., Ltd , Taipei, Taiwan³

Purpose

Radium-223 is a first-of-its-kind FDA-approved bone-targeting internal alpha particle-emitting radiotherapeutic agent that positively impacts delay in symptomatic skeletal events, and quality of life. Apart from this several studies demonstrated that it can effectively improve overall survival. Thus, the current meta-analysis aims to create a new survival curve based on inclusion studies to better understand Ra-223's efficacy of overall survival.

Materials and Methods

Two independent authors performed a comprehensive and systematic literature search of the PubMed/MEDLINE and Cochrane Library databases and reviewed the literature on the Radium-223 effect among mCRPC patients. This search was updated to March 10, 2023.  We created the new survival curve of overall survival time after Ra-223 treatment in all included studies, we first extracted the survival time and probability from the Kaplan-Meier curve and the summary survival curve by the risk of the event over time using metaSURV of the R package in the included studies. Finally, the studies included both Ra-223 and placebo, both Ra-223 combination and single therapy, or Ra-223 treatment both complete and incomplete, the median survival ratio (MSR) was conducted through log transformation and calculated with an effect test.

Results

Thirty-four studies for receiving radium-223 therapy were included to create a new survival curve. The number at risk was 6919 patients and of events was 3788 patients. The patient`s median (range) of age was 73.0 (68-76.8). Before radium-223 therapy, 53.33% of patients received androgen deprivation therapy (ADT) and 46.55% of patients received chemotherapy (C/T). The median (range) follow-up time was 14 months (7.5-68.1 months).

In the current meta-analysis, the pooling median overall survival after receiving radium-223 of included studies was a median of 16.63 months (95% CI 14.26-19.94 months). Compared with placebo, the pooling medina of overall survival after receiving radium-223 was not significant difference [Ra-223 vs placebo 15.08 month (95% CI 10.92-22.73 months) vs 14.22 months (95% CI 10.25-22.08 months), MSR 1.38 (95% CI 0.89-2.15), p =0.154].

In addition, the pooling median overall survival of Ra-223 combination with other ADT or C/T was longer than Ra-223 monotherapy [Ra-223 combination therapy vs monotherapy 15.64 months (95% CI 13.34-18.29 months) vs 14.60 months (95% CI 12.68-16.76 months), MSR 1.22 (95% CI 1.03-1.46), p = 0.0248). Finally, compared with incomplete Ra-223 therapy, the pooling median of overall survival in completed Ra-223 therapy was longer [6.98 months (95% CI 5.71-8.37months) vs 20.22 months (95% CI 17.14-27.76 months), MSR 3.07 (95% CI 1.97-4.81), p < 0.001].

Conclusions

In the current meta-analysis, the overall survival can improve when the mCRPC patient receiving Ra-223 therapy has completed 5-6 cycles of therapy or combined with ADT or C/T therapy. However, the overall survival was no difference between receiving Ra-223 and placebo therapy.