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

摘要

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 e50% 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-na譭 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.