Evaluation of Response to Enzalutamide Consecutively After Abiraterone Acetate/Prednisone Failure in Patients With Metastatic Castration-resistant Prostate Cancer

Clin Genitourin Cancer. 2018 Dec;16(6):429-436. doi: 10.1016/j.clgc.2018.08.002. Epub 2018 Aug 17.

Abstract

Introduction: Treatment of metastatic castration-resistant prostate cancer (mCRPC) has evolved significantly during the past decade, and the preferred combination and/or sequence of these treatments remains controversial. In this retrospective study, we explored clinical and pathologic factors that could predict response to consecutive treatment with enzalutamide (ENZA) after disease progression (PD) on abiraterone acetate and prednisone (AA/P).

Patients and methods: Data were collected from 40 consecutive patients with mCRPC who were treated with ENZA without other interim therapy after progression on AA/P.

Results: The median time from prostate cancer initial diagnosis to AA/P treatment was 6.2 (range, 0.9-16.3) years. The median prostate-specific antigen (PSA) progression-free survival (PSA-PFS) from treatment initiation was 8.5 months (95% confidence interval [CI], 7.1-10.1 months) and 2.3 months (95% CI, 1.8-3.4 months) on AA/P and ENZA, respectively. The median time to PD from treatment initiation was 9.7 months (95% CI, 7.1-12.4 months) and 3 months (95% CI, 2.3-4.1 months) on AA/P and ENZA, respectively. The correlations were weak between the best percent change in PSA on ENZA and time from diagnosis to AA/P initiation, best absolute or percentage change in PSA on AA/P, time to PSA progression or PD on AA/P. Patients with longer than the median duration of treatment with AA/P (11.73 months) had longer PSA-PFS on ENZA (median 2.8 vs. 1.9 months; P = .035).

Conclusions: In this retrospective analysis, we did not find any clinical or pathologic factors associated with response to ENZA administered consecutively after AA/P. Patients with longer than median AA/P treatment duration had longer PSA-PFS on ENZA. Further evaluations and validation are greatly needed.

Keywords: AR-Targeted therapy; CRPC; Response prediction; Second-line hormonal therapy; Treatment sequencing.

MeSH terms

  • Abiraterone Acetate / pharmacology
  • Abiraterone Acetate / therapeutic use*
  • Aged
  • Androstenes / pharmacology
  • Androstenes / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzamides
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Humans
  • Kallikreins
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nitriles
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / pharmacology
  • Phenylthiohydantoin / therapeutic use
  • Prednisone / pharmacology
  • Prednisone / therapeutic use
  • Progression-Free Survival
  • Prostate-Specific Antigen
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Retrospective Studies
  • Time Factors
  • Treatment Failure
  • Treatment Outcome

Substances

  • Androstenes
  • Benzamides
  • Nitriles
  • Phenylthiohydantoin
  • enzalutamide
  • Kallikreins
  • Prostate-Specific Antigen
  • Abiraterone Acetate
  • abiraterone
  • Prednisone