Switch from abiraterone plus prednisone to abiraterone plus dexamethasone at asymptomatic PSA progression in patients with metastatic castration-resistant prostate cancer

BJU Int. 2019 Feb;123(2):300-306. doi: 10.1111/bju.14511. Epub 2018 Sep 4.

Abstract

Objective: To evaluate the effects of switching from prednisone (P) to dexamethasone (D) at asymptomatic prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA).

Materials and methods: Among 93 patients treated with AA between January 2013 and April 2016 in our institution, 48 consecutive asymptomatic patients with mCRPC, who experienced biochemical progression on treatment with AA+P 10 mg/day, were included. A corticosteroid switch to AA+D 0.5 mg/day at PSA increase was administered until radiological and/or clinical progression. The primary endpoint was progression-free-survival (PFS). A prognostic score based on independent prognostic factors was defined.

Results: The median time to PSA progression on AA+P was 8.94 months. The median PFS on AA+D and AA+corticosteroids (P then D) was 10.35 and 20.07 months, respectively. A total of 56.25% of patients showed a decrease or stabilization in PSA levels after the switch. In univariate analysis, three markers of switch efficiency were significantly associated with a longer PFS: long hormone-sensitivity duration (≥5 years; median PFS 16.62 vs 4.17 months, hazard ratio [HR] 0.30, 90% confidence interval [CI] 0.16-0.56); low PSA level at the time of switch (<50 ng/mL; median PFS 15.21 vs 3.86 months, HR 0.33, 90% CI 0.18-0.60); and short time to PSA progression on AA+P (<6 months; median PFS 28.02 vs 6.65 months, HR 0.41 (90% CI 0.21-0.81). In multivariate analysis, hormone sensitivity duration and PSA level were independent prognostic factors.

Conclusion: A steroid switch from P to D appears to be a safe and non-expensive way of obtaining long-term responses to AA in selected patients with mCRPC. A longer PFS has been observed in patients with previous long hormone sensitivity duration, and/or low PSA level and/or short time to PSA progression on AA+P.

Keywords: #PCSM; #ProstateCancer; abiraterone; corticoid; dexamethasone; genitourinary tumours; metastatic castration-resistant prostate cancer.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstenes / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asymptomatic Diseases
  • Dexamethasone / administration & dosage
  • Disease Progression
  • Drug Substitution
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prednisone / administration & dosage
  • Prognosis
  • Progression-Free Survival
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms, Castration-Resistant / blood*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Retrospective Studies

Substances

  • Androstenes
  • Dexamethasone
  • Prostate-Specific Antigen
  • abiraterone
  • Prednisone