Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone.

Abstract

BACKGROUND:

The optimal sequencing of the multiple active agents now available for metastatic castration-resistant prostate cancer (mCRPC) is unclear. Prior reports have suggested diminished responses to sequential lines of androgen receptor (AR)-targeted therapies, but it is unknown whether subsequent taxane-based chemotherapy may be more effective than sequential AR-targeting treatment. We sought to evaluate the clinical activity of enzalutamide versus docetaxel in men with mCRPC who progressed on abiraterone.

METHODS:

We performed a single-institution retrospective analysis of consecutive mCRPC patients who had progressed on abiraterone therapy and subsequently received either enzalutamide (n=30) or docetaxel (n=31). We evaluated clinical outcomes including prostate-specific antigen decline of >30% (PSA30) or >50% (PSA50), PSA-progression-free survival (PSA-PFS), and clinical/radiographic PFS. We performed multivariable modeling to control for baseline and on-treatment differences between groups.

RESULTS:

Compared to subjects who received enzalutamide post-abiraterone, subjects who received docetaxel post-abiraterone had more bone metastases, more visceral metastases, higher baseline PSA, and had more frequent PSA tests while on-treatment. There were no significant differences in PSA30 (41% for enzalutamide vs. 53% for docetaxel) or PSA50 (34% vs. 40%) response rates between the two groups; there remained no difference after stratifying by presence/absence of prior response to abiraterone. Median PSA-PFS was 4.1 versus 4.1 months for the enzalutamide and docetaxel cohorts, respectively (HR 1.35, 95% CI, 0.53-3.66, P=0.502). Median PFS was 4.7 versus 4.4 months, respectively (HR 1.44, 95% CI, 0.77-2.71, P=0.257). PSA-PFS and PFS did not differ after stratifying by prior response to abiraterone. In multivariable analyses, there were no significant differences in PSA-PFS or PFS between the two groups.

CONCLUSIONS:

Treatment with either enzalutamide or docetaxel produced modest PSA responses and PFS intervals in this abiraterone-pretreated mCRPC population. In this retrospective study with small sample size, no significant differences in outcomes were observed between groups. Therefore, either enzalutamide or docetaxel may be a reasonable option in men who have progressed on abiraterone.

• Authors: Daniel L Suzman, Brandon Luber, Michael T Schweizer, Rosa Nadal, Emmanuel S Antonarakis
• Journal: The Prostate (Prostate) Vol. 74 Issue 13 Pg. 1278-85 (Sep 2014) ISSN: 1097-0045 [Electronic] United States
• PMID: 25053178 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Androstenes
• Androstenols
• Antineoplastic Agents
• Benzamides
• Nitriles
• Taxoids
• Docetaxel
• Phenylthiohydantoin
• enzalutamide
• abiraterone

Topics

• Adenocarcinoma (drug therapy, secondary)
• Aged
• Androstenes
• Androstenols (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Benzamides
• Bone Neoplasms (drug therapy, secondary)
• Disease Progression
• Docetaxel
• Drug Resistance, Neoplasm
• Humans
• Male
• Middle Aged
• Nitriles
• Phenylthiohydantoin (analogs & derivatives, therapeutic use)
• Prostatic Neoplasms, Castration-Resistant (drug therapy)
• Retrospective Studies
• Taxoids (therapeutic use)
• Treatment Outcome