The Influence of Prior Abiraterone Treatment on the Clinical Activity of Docetaxel in Men with Metastatic Castration-resistant Prostate Cancer

BackgroundTaxanes 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.ObjectiveTo evaluate docetaxel efficacy after abiraterone treatment in CRPC patients.Design, setting, and participantsThis 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 analysisThe 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 limitationsMen 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.ConclusionsMen 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 summaryWe 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.