The influence of prior novel androgen receptor targeted therapy on the efficacy of cabazitaxel in men with metastatic castration-resistant prostate cancer

Eur J Cancer. 2015 Nov;51(17):2562-9. doi: 10.1016/j.ejca.2015.07.037. Epub 2015 Aug 13.

Abstract

Introduction: The treatment armamentarium for metastatic castration-resistant prostate cancer (mCRPC) has expanded with the introduction of several new therapies. In this treatment continuum, it is unclear whether the efficacy of cabazitaxel is affected by prior novel androgen receptor targeted therapies (ART) such as abiraterone and enzalutamide. In this study, we investigated the influence of prior ART on the efficacy of cabazitaxel in men with mCRPC.

Patients and methods: Data from an ongoing multicentre, phase II trial were used comprising 114 men with mCRPC treated with cabazitaxel in the post-docetaxel setting. The primary endpoints of the current analysis were prostate-specific antigen (PSA) response (⩾ 50%), and overall survival (OS). Univariate and multivariable analyses were conducted to investigate the influence of prior ART on the efficacy of cabazitaxel.

Results: From the 114 patients included in this analysis, 44 men received prior ART and 70 men did not receive prior ART before treatment with cabazitaxel. PSA response rates while on cabazitaxel treatment were similar in patients with and without prior ART (34% versus 40%, respectively, P = 0.53). Likewise, median OS was not significantly different between men with and without prior ART (13.0 versus 14.0 months, respectively, logrank P = 0.65). In multivariable analysis, the only variables significantly associated with OS were performance status, serum albumin and alkaline phosphatase.

Conclusion: Our study showed that prior treatment with ART may not influence the efficacy of cabazitaxel in men with mCRPC. With emerging evidence of cross-resistance in the treatment of mCRPC, cabazitaxel provides a good treatment option irrespective of prior ART.

Keywords: Abiraterone; Cabazitaxel; Enzalutamide; Metastatic castration-resistant prostate cancer; Taxanes.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstenes / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzamides
  • Disease-Free Survival
  • Docetaxel
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods*
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Nitriles
  • Phenylthiohydantoin / administration & dosage
  • Phenylthiohydantoin / analogs & derivatives
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / metabolism
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Receptors, Androgen / metabolism*
  • Taxoids / administration & dosage
  • Treatment Outcome

Substances

  • AR protein, human
  • Androstenes
  • Benzamides
  • Nitriles
  • Receptors, Androgen
  • Taxoids
  • Docetaxel
  • Phenylthiohydantoin
  • cabazitaxel
  • enzalutamide
  • Prostate-Specific Antigen
  • abiraterone