The influence of prior abiraterone treatment on the clinical activity of docetaxel in men with metastatic castration-resistant prostate cancer

Abstract

Background: Taxanes may partly mediate their effect in castration-resistant prostate cancer (CRPC) through disruption of androgen-receptor trafficking along microtubules. This raises the possibility of cross-resistance between androgen-directed agents and docetaxel.

Objective: To evaluate docetaxel efficacy after abiraterone treatment in CRPC patients.

Design, setting, and participants: This was a single-institution, retrospective analysis in CRPC patients (N=119) who either received abiraterone before docetaxel (AD) (n=24) or did not receive abiraterone before docetaxel (docetaxel-only; n=95). Men initiated docetaxel between December 2007 (the date abiraterone was first used at our center) and May 2013.

Outcome measurements and statistical analysis: The primary efficacy end points were prostate-specific antigen progression-free survival (PSA-PFS) and clinical/radiographic progression-free survival (PFS) on docetaxel. Differences between groups were assessed using univariate and multivariable analyses.

Results and limitations: Men in the AD group had a significantly higher risk for progression than those in the docetaxel-only group. Median PSA-PFS was 4.1 mo in the AD group and 6.7 mo in the docetaxel-only group (p=0.002). Median PFS was also shorter in the AD group (4.4 mo vs 7.6 mo; p=0.003). In multivariable analysis, prior abiraterone treatment remained an independent predictor of shorter PSA-PFS (hazard ratio [HR]: 3.48; 95% confidence interval [CI], 1.36-8.94; p=0.01) and PFS (HR: 3.62; 95% CI, 1.41-9.27; p=0.008). PSA declines ≥50% were less frequent in the AD group (38% vs 63%; p=0.02). The small size and retrospective nature of this study may have introduced bias.

Conclusions: Men receiving abiraterone before docetaxel were more likely to progress on docetaxel and less likely to achieve a PSA response than abiraterone-naïve patients. Cross-resistance between abiraterone and docetaxel may explain these findings; however, larger, more definitive studies are still needed to confirm this.

Patient summary: We examined the efficacy of docetaxel in castration-resistant prostate cancer patients who either did or did not receive prior abiraterone. We found that men receiving abiraterone before docetaxel were less likely to achieve a PSA response and were more likely to progress sooner on docetaxel than abiraterone-untreated patients. This may be due to cross-resistance.

Keywords: Abiraterone; Activity; Docetaxel; Efficacy; Progression-free survival; Prostate cancer.

Fig. 1

Prostate cancer clinical states model (adapted from Scher et al [4]).

Fig. 2

Kaplan-Meier curves for (a) progression-free survival (PFS) and (b) prostate-specific antigen PFS during treatment with docetaxel. Abiraterone→docetaxel = abiraterone-pretreated group; CI = confidence interval; docetaxel-only = abiraterone-naïve group; PSA = prostate-specific antigen.

Fig. 3

Waterfall plots depicting the maximal prostate-specific antigen (PSA) decline (or minimum increase for those without a PSA decline) after docetaxel treatment for the (a) abiraterone-naïve (docetaxel only) and (b) abiraterone-pretreated cohort. * Bar is truncated due to >100% PSA increase. CI = confidence interval.