Tumour responses following a steroid switch from prednisone to dexamethasone in castration-resistant prostate cancer patients progressing on abiraterone

Abstract

Background:Abiraterone is a CYP17A1 inhibitor that improves survival in castration-resistant prostate cancer (CRPC). Abiraterone is licensed in combination with prednisone 5 mg twice daily to prevent a syndrome of secondary mineralocorticoid excess. We hypothesised that a ‘steroid switch' from prednisone to dexamethasone would induce secondary responses in patients progressing on abiraterone and prednisone 5 mg b.i.d.Methods:We performed a ‘steroid switch' in patients with CRPC at PSA progression on abiraterone and prednisolone. Patients were monitored for secondary declines in PSA, radiological tumour regression and toxicity.Results:A retrospective analysis of 30 CRPC patients who underwent a steroid switch from prednisolone to dexamethasone while on abiraterone was performed. A total of six patients (20%) had a ⩾50% PSA decline that was confirmed by a second PSA level at least 3 weeks later. In all, 11 patients (39.2%) had a confirmed ⩾30% PSA decline. Median time to PSA progression on abiraterone and dexamethasone was 11.7 weeks (95% CI: 8.6–14.8 weeks) in the whole cohort and 27.6 weeks (95% CI: 14.5–40.7 weeks) in patients who achieved a confirmed 50% PSA decline. Nine patients had RECIST evaluable disease: two of these patients had RECIST partial response, six patients had stable disease and one patient had progressive disease at the first imaging assessment. Treatment was well tolerated, with no grade 3 and grade 4 adverse events. One patient had to be reverted to prednisolone because of grade 2 hypotension.Conclusions:Durable PSA responses occur in up to 40% of patients following a ‘steroid switch' for PSA progression on abiraterone and prednisone. Studies are ongoing to elucidate the mechanisms underlying this response.

Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017

“…In these patients abiraterone was continued and prednisone was switched to 0.5-1 mg dexamethasone/d. There were responses demonstrated by PSA as well as by imaging [77,78]. The level of evidence for this intervention is low.…”

A Randomised Phase 2 Trial of Dexamethasone Versus Prednisolone in Castration-resistant Prostate Cancer

“…In an early study of abiraterone treated without concomitant steroids, the addition of dexamethasone on progression was capable of inducing PSA responses [18]. Recently, the change from prednisolone to dexamethasone in patients progressing on abiraterone showed PSA declines and RECIST responses after switching steroids [19].…”

Reconsideration of Hormonal Therapy in the Era of Next‐ Generation Hormonal Therapy

“…Furthermore, the PSA response rates, defined as a 50% or more reduction in PSA levels associated with dexamethasone and prednisolone were reported to be 47% and 24% (P = 0.05), respectively, in CRPC patients during a randomized Phase II trial [67]. Based on this, a hypothesis that a "steroid switch" from prednisone to dexamethasone would be effective in the treatment of CRPC patients with disease progression under abiraterone and prednisone treatment has been suggested [72]. In fact, one retrospective study of 30 CRPC patients who underwent such a "steroid switch" while abiraterone was administered, showed that durable PSA responses occurred in up to 40% of the patients [72].…”