Switch from abiraterone + prednisone to abiraterone + dexamethasone after PSA progression under abiraterone + prednisone in asymptomatic metastatic castration-resistant prostate cancer (mCRPC) patients

Abstract

Background: Abiraterone acetate (AA) is active in mCRPC. AA is usually administrated with prednisone (P) to prevent mineralocorticoid excess until radiological or symptomatic progression regardless of PSA. A switch from P to dexamethasone (D) was reported to induce tumor responses in patients progressing on AA+ P. This prospective study was designed to evaluate outcome of patients (pts) with asymptomatic PSA progression on AA + P after the switch, and to determine predictive factors of switch efficiency. Methods: Among 120 pts treated with AA between Jan 2013 and Apr 2016 in our institution, 48 consecutive asymptomatic mCRPC pts, progressing only biologically on AA + P 10mg daily, were switched to AA + D 0.5mg daily at the time of PSA increase. AA + D was administered until radiological and/or symptomatic progression. Results: Median age at switch was 82 +/- 7yrs (57-92). Median time of hormonosensitivity was 82 months (mo). 7 pts previously received docetaxel. Median time to PSA progression on AA + P was 8.6 mo. Median (med) follow-up time from switch was 14 mo. Actuarial median PFS's on AA + D and on AA+ corticosteroids (P then D) were 14.5 and 23.1 mo, respectively. 45.8% of pts had a PSA decrease after the switch. Univariate prognostic factors of switch efficiency were long hormonosensitivity duration (> 5 yrs; med PFS 16.6 vs 3.9 mo, p = 0.0012, HR : 4.46 (1.8 - 11.03)), low PSA level at switch (< 50 ng/ml; med PFS 15.2 mo vs 3.8 mo, p= 0.0041, HR 3.23 (1.45 - 7.20)), and short time to PSA progression on AA + P (<6 mo; med PFS undefined vs 7.7 mo, p = 0.025, HR 2.52 (1.12 - 5.68)). When 1 point per worse prognostic factor is allocated, score 0-1 and 2-3 were obtained in 23 and 25 pts, respectively. AA + D PFS's according to score 0-1 vs 2-3 were highly statistically different (med PFS undefined vs 3.8, p < 0.0001, HR 6.12 (2.75 - 13.63)). Conclusions: Switch from P to D is able to reverse biological resistance to AA + P in almost half of mCRPC pts. Lasting PFS have been observed in pts with previous long hormonosensitivity, and/or low PSA level and/or short time to PSA progression on AA + P. This switch deserves further evaluation in randomized studies.