AbiDex: Retrospective U.K. analysis of steroid switching in patients with progression of mCRPC treated with abiraterone acetate.
Authors: Muller Dan , Leaper Alice , Yadollahi Sina , Teasdale Kim , Irfan Shoaib , Theivendrampillai Shenthiuiyan , Elbayyar Omar , Wheater Matthew 
Published: February 2022

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Background: Abiraterone acetate (AA) is a mainstay of treatment for metastatic castrate resistant prostate cancer (mCRPC). Due to inhibition of glucocorticoid synthesis, AA can cause mineralocorticoid excess which is suppressed by the co-administration of a glucocorticoid. Prednisolone (P) is widely used to counter the side effects of AA. There is an expanding body of retrospective evidence that dexamethasone (D) may be a more suitable partner for AA and on biochemical progression with AA+P, a ‘steroid switch’ to AA+D may be efficacious in regaining PSA control. Methods: Retrospective analysis patients treated with AA at a UK, tertiary cancer centre, were included to a data cutoff of 28th April 2021. Those who had undergone a steroid switch were identified and baseline data of demographics and clinical history were collected, as well as biochemical and radiological data whilst on AA. Analysis was conducted using SPSS. Biochemical progression free survival (bPFS) analysis was conducted using the Kaplan-Meier U test. Response steroid switch and survival when compared to potential predictive factors was analysed using binomial logistic and Cox regression models. Results: Thirty-three patients were treated with AA and received a steroid switch, AA+P(5mg BD) to AA+D(0.5mg OD) between 2012 and data cutoff. The median age at diagnosis was 71, the majority had Gleason 7 disease (7-10). Nine patients had received prior Docetaxel chemotherapy. Four patients failed to respond to AA+P; three of which achieved a biochemical response after steroid switch. Following switch to AA+D, 24 (73%) of patient achieved a rebound biochemical response after progression on AA+P, of those who achieved a response, 4 (12%) achieved a >30% reduction in PSA, and 12( 36%) achieved a >50% reduction in PSA. The median bPFS before and after steroid switch was 9 (AA+P) vs 19 (AA+P&+D) months (HR 0.28; 95% CI 0.16-0.51; p<.001). Analysis of response to steroid switch showed no significant correlation between response and any investigated clinical factor. A raised ALP(>130U/L) on commencing AA+D predicted for a poorer bPFS (HR 2.4; 95% CI 1.1-5.5; p=0.038) and OS (HR 3.2; 95% CI 1.2-8.5; p=0.02). Conclusions: A steroid switch from AA+P to AA+D on biochemical progression is gaining more evidence as a beneficial technique to improve duration of treatment on AA. This study again suggests that bPFS is significantly improved by a steroid switch from P to D. Although negative in this study, several predictive models have been reported to help clinical selection of who may benefit most from a switch. Despite this, there is no official guidance or consensus on when and how a steroid switch should be used and whether this improves overall survival of those with mCRCP. Further randomised, prospective studies are needed to to better define the utility of AA+D, including in the first line setting.