764PD - A Randomised Phase Ii Trial of Dexamethasone Versus Prednisolone in Castration Resistant Prostate Cancer

Abstract

ABSTRACT Aim: Prednisolone is commonly used to treat castrate-resistant prostate cancer (CRPC). We hypothesised that dexamethasone would have superior antitumour activity to prednisolone. Methods: A randomised, open-label, Phase II trial of prednisolone 5mg bid versus dexamethasone 0.5mg once/day was pursued. All patients had castrate levels of testosterone on androgen deprivation therapy, PSA progression after anti-androgen withdrawal, baseline PSA > 5ng/ml and no prior treatment for CRPC with either corticosteroids or chemotherapy. The primary end point was PSA response, defined as 50% decline confirmed at least 4 weeks later. Secondary endpoints included time to PSA progression, radiologic response rate using RECIST, and safety. Patients crossed over from prednisolone to dexamethasone at progression. The planned sample size was 72, based on 80% power to detect a response rate of 60% for dexamethasone versus 20% for prednisolone, with a 2-sided alpha of 0.05. Results: 75 patients were randomised. In patients evaluable for response (with at least two on-treatment PSA levels), the PSA response rates were 47% (16/34) for dexamethasone and 24% (8/33) for prednisolone (p = 0.05). Median time to PSA progression was 9.7 months on dexamethasone versus 5.1 months on prednisolone (HR 1.6, 95%CI: 0.9-2.8). In 38 patients with measurable disease, the response rate by RECIST was 15% (3/20) and 6% (1/18) for dexamethasone and prednisolone, respectively (p = 0.6). Of 19 patients who crossed over at PSA progression on prednisolone, seven (37%) had a confirmed PSA response to dexamethasone. Both prednisolone and dexamethasone were well tolerated with no significant differences in safety and tolerability. Conclusions: Dexamethasone may be more active than prednisolone in CRPC. In the absence of more definitive trials, dexamethasone should be used in preference to prednisolone. Disclosure: C. Parker: I have received honoraria from Astellas, Bayer, BNIT, Janssen, Sanofi-Aventis and Takeda. I have received research funding fom Bayer; R. Ahiabor: employed by Pharmacyclics; D. Dearnaley: has received honoraria for advisory boards and served as a consultant for Takeda, Amgen, Astellas and Succinct Healthcare. Prof Dearnaley is on the Institute's Rewards to Inventors list for abiraterone acetate. All other authors have declared no conflicts of interest.