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.

Keywords: abiraterone; docetaxel; enzalutamide; prostate cancer; sequencing.

© 2014 Wiley Periodicals, Inc.

Figures

Figure 1

Waterfall plot depicting the maximal prostate-specific antigen (PSA) decline (or minimum increase for those without a PSA decline) after initiation of enzalutamide or docetaxel. Dashed lines indicated PSA30 and PSA50 responses. *Bar is truncated due to >100% PSA increase.

Figure 2

Kaplan-Meier curves for (A) PSA-progression-free survival (PSA-PFS) and (B) clinical/radiographic progression-free survival (PFS) during treatment with either enzalutamide or docetaxel.

Figure 3

Kaplan-Meier curves for (A) PSA-PFS and (B) PFS in patients refractory to prior abiraterone (i.e. failure to achieve PSA30); and (C) PSA-PFS and (D) PFS in patients with prior response to abiraterone (>30% PSA decline).