BERKELEY, CA (UroToday.com) - Despite significant advances in treatment of metastatic castration-resistant prostate cancer (mCRPC), questions about optimal sequencing of systemic therapy and whether cross-resistance occurs between different drugs remain largely unanswered.
Previously, it was reported by a group from the Royal Marsden that docetaxel is inactive in patients who do not attain a ≥ 50% PSA decline on abiraterone acetate. This led the authors to speculate on the possibility of cross-resistance between abiraterone and docetaxel. The objective of this study was to examine whether biochemical response to abiraterone is linked to efficacy of subsequent docetaxel treatment. We identified 86 patients treated with docetaxel post-abiraterone at 3 large Canadian cancer centres. In contrast to the findings from the Royal Marsden study, we saw no significant differences in confirmed PSA decline ≥ 50% (38% vs. 36% vs. 31%, P = 0.86), median progression-free survival (4.04 months vs. 3.94 months vs. 4.24 months, P = 0.43) and median OS (11.86 months vs. 15.38 months vs. 11.00 months, P = 0.56) on docetaxel for patients with no PSA decline, < 50% decline and ≥ 50% decline respectively on abiraterone. Similar findings were reported in two other retrospective studies from UCSF and Johns Hopkins.
Although all of the studies in question are retrospective and comprise relatively small numbers of patients, the available evidence does indicate that prior response to abiraterone should not be used to guide patient selection for subsequent treatment with docetaxel. Nevertheless, prospective studies are needed to identify optimal treatment sequencing and investigate mechanisms of cross-resistance in mCRPC.
- Mezynski J, et al. Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance? Ann Oncol. 2012;23:2943-7
- Aggarwal R, et al. Response to Subsequent Docetaxel in a Patient Cohort With Metastatic Castration-Resistant Prostate Cancer After Abiraterone Acetate Treatment. Clin Genitourin Cancer. 2014;12(5):e167-72
- Schweizer M. T et al. The Influence of Prior Abiraterone Treatment on the Clinical Activity of Docetaxel in Men with Metastatic Castration-resistant Prostate Cancer. Eur Urol. 2014;66(4):646-52
Arun Azad, MBBS, PhD, FRACP as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
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