Both α-emitting and β-emitting bone-targeted radioisotopes (RIs) have revolutionised the treatment of metastatic castration-resistant prostate cancer (CRPC). However, only one phase 3 randomised clinical trial has demonstrated an overall survival (OS) with radioisotopes vs standard of care. No head-to-head comparison between α-emitting and β-emitting RIs has been done.
Now a new review published in JAMA Oncology examined data from eligible studies identified through a search of PubMed, Cochrane Library, ClinicalTrials.gov, and meeting proceedings between January 1993 and June 2013.
Based on six randomised clinical trials including 2081 patients, RI use was significantly associated with OS compared with no RI use (HR 0.86; 95% CI 0.77-0.95; P=0.004) with high heterogeneity. This association disappeared when using a fixed-effects (FE) model (HR 0.80; 95% CI 0.61-1.06; P=0.12).
The authors say the heterogeneity can be explained not only by the type of RI and also by the inclusion of two outlier trials that included 275 patients and showed a significant OS benefit was radium-223 (HR 0.70; 95% CI 0.58-0.83) but was not significant with strontium-89 (HR 0.96; 95% CI 0.84-1.10) (P for interaction =0.004).
Excluding the outlier trials led to an overall HR of 0.82 (95% CI 0.73-0.92; P<0.001) using an FE model and an HR of 0.80 (95% CI 0.65-0.99; P=0.04) using a random-effects (RE) model. The HR for symptomatic skeletal event (SSE)-free survival was 0.81 (95% CI 0.69-0.93; P=0.004) when using an FE model and 0.76 (95% CI 0.58-1.01; P=0.06) when using an RE model.
There were more haematological toxic effects with RI use compared with no RI use (OR 1.48; 95% CI 1.17-1.88; P=0.001).
The authors concluded that in metastatic CRPC, bone-targeted α-emitting but not β-emitting RIs delivered significant improvement of OS and SSE-free survival, however caution is advised regarding the generalisability of these results, given the between-trial heterogeneity.
