The sequential use of abiraterone and enzalutamide in metastatic castrate resistant prostate cancer patients: Experience from seven U.K. centers.

Abstract

125 Background: Phase III studies have demonstrated survival benefits from abiraterone (Abi), and enzalutamide (Enz) following disease progression in metastatic castrate resistant prostate cancer (mCRPC). Abi is now available for treatment of mCRPC in the UK in patients previously treated with docetaxel. Enz has recently become available, via the UK cancer drugs fund (CDF), for progressive disease post docetaxel, prior to exposure to Abi. There has been no randomised trial on sequential usage of Enz post-Abi. We therefore, report the experience of hospitals in Coventry, Cardiff, and five centers in Birmingham. Methods: We searched the pharmacy database for patients who have received Enz as part of an early access scheme, and identified 79 patients who started treatment between the August 2012 and April 2013. A detailed notes review was carried out of these patients. Results: Median age was 74 (range of 55 to 87). All patients had received hormone androgen deprivation therapy and taxane chemotherapy (docetaxel and/or cabazitaxel) 75 patients had received previous Abi, 62 of these patients receiving Abi as the last treatment prior to Enz. The mean time to progression (TTP) for Abi in these 62 patients was 37.44 weeks (range 4 to 104). At the time of submission 55 patients had stopped Enz due to prostate-specific antigen progression with a mean TTP of 15.87 weeks and 28 patients had died. Conclusions: The AFFIRM study demonstrated TTP of 36 weeks in patients post-docetaxel. In this audit of patients receiving Enz post-Abi the TTP was only 15.87 weeks, suggesting possible reduced efficacy in patients receiving Enz post-Abi and docetaxel. Trials are underway comparing Abi alone or in combination with Enz which may improve efficacy.

Metastatic castration-resistant prostate cancer: new therapies, novel combination strategies and implications for immunotherapy

“…108 In certain cases, administration of agents simultaneously rather than sequentially may be more efficacious. Given that preliminary results from a trial in which enzalutamide was given after abiraterone acetate and docetaxel suggested possible reduced efficacy in mCRPC patients, 109 it is hypothesized that simultaneous administration of these agents may lead to improved benefit, a combination that is currently being evaluated clinically in mCRPC (NCT01650194). 110 …”

Efficacy, quality of life, and safety of cabazitaxel in Canadian metastatic castration-resistant prostate cancer patients treated or not with prior abiraterone

“…For treatment sequences involving enzalutamide or abiraterone as a second-line agent following the opposite agent, several other studies have reported that 17-28% of patients achieved a PSA response. [26][27][28][29][30][31][32][33][34] A report from Schnadig et al showed that more patients reached a third-line treatment if they received docetaxel followed immediately by cabazitaxel, compared to docetaxel followed by abiraterone. 35 This retrospective analysis in 667 post-docetaxel mCRPC patients showed that 31% of patients who received cabazitaxel second-line received abiraterone in third-line, compared to only 12% of patients who received cabazitaxel third-line if they received abiraterone second-line.…”

Enzalutamide After Docetaxel and Abiraterone Acetate Treatment in Prostate Cancer: A Pooled Analysis of 10 Case Series

“…Of these, 3 original articles and 7 abstracts were selected for inclusion in this pooled analysis ( Figure 1 and Table 1). 11,12,[14][15][16][17][18][19][20][21] The primary outcomes were > 50% PSA RR, activity according to previous AA response, and median PFS (or TTP). The secondary outcome was safety and the median duration of treatment.…”