Enzalutamide in Castration-resistant Prostate Cancer Patients Progressing After Docetaxel and Abiraterone

• Published in: European urology Vol. 65; no. 1; pp. 30 - 36
• Main Authors: Schrader, Andres Jan, Boegemann, Martin, Ohlmann, Carsten-H, Schnoeller, Thomas J, Krabbe, Laura-Maria, Hajili, Turkan, Jentzmik, Florian, Stoeckle, Michael, Schrader, Mark, Herrmann, Edwin, Cronauer, Marcus V
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.01.2014; Elsevier
• Subjects: Abiraterone; Aged; Aged, 80 and over; Androstenes; Androstenols - therapeutic use; Antineoplastic Agents - therapeutic use; Biochemical failure; Biological and medical sciences; Cross-resistance; Disease Progression; Docetaxel; Enzalutamide; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; MDV3100; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Phenylthiohydantoin - analogs & derivatives; Phenylthiohydantoin - therapeutic use; Pilot Projects; Prostate-Specific Antigen - blood; Prostatic Neoplasms, Castration-Resistant - blood; Prostatic Neoplasms, Castration-Resistant - drug therapy; Sequential therapy; Taxoids - therapeutic use; Treatment Failure; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urology; MDV3100; Enzalutamide; Sequential therapy; Abiraterone; Biochemical failure; Cross-resistance; Antineoplastic agent; Nephrology; Prostate disease; Antihormone; Biochemical recurrence; Urology; Castration; Sequential; Taxane derivatives; Cross resistance; Antimitotic; Male genital diseases; Human; Urinary system disease; Docetaxel; Antiandrogen; Malignant tumor; Treatment; Prostate cancer; Cancer
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2013.06.042

Abstract Background Abiraterone, an androgen synthesis inhibitor, has been successfully used in the treatment of castration-resistant prostate cancer (CRPC) for 2 yr. Enzalutamide is a second-generation nonsteroidal antiandrogen that has recently been approved for the same indication. Objective This is the first study to evaluate the effectiveness of enzalutamide after failure of abiraterone. Design, setting, and participants Thirty-five patients were identified as having received sequential therapy with abiraterone followed by enzalutamide. All patients had undergone prior docetaxel chemotherapy, and no patient had received ketoconazole. Outcome measurements and statistical analysis Posttreatment changes in prostate-specific antigen (PSA) were used to determine the activity of enzalutamide in patients who had received prior abiraterone. Results and limitations The median duration of abiraterone treatment was 9.0 mo (range: 2.0–19.0 mo). Of the 35 patients, 16 (45.7%) achieved a >50% decline in PSA, and 14 (40%) had a rising PSA as the best response. The median duration of subsequent enzalutamide treatment was 4.9 mo (Kaplan-Meier estimate; 95% confidence interval [CI], 2.4–7.4). Seven of 16 CRPC patients who were initially abiraterone-sensitive (43.8%) and 3 of 19 CRPC patients who were initially abiraterone-insensitive (15.8%) showed a >50% PSA decline while taking enzalutamide. Of the 35 patients, 17 (48.6%) were primarily enzalutamide-resistant and showed a rising PSA as the best response. Median time to progression was 4.0 mo (95% CI, 2.0–6.0) for 18 of 35 patients with at least one declining PSA value while taking enzalutamide (51.4%). Of the 17 patients who were assessable radiologically, only 1 (2.9%) attained a confirmed partial response. Small sample size was the major limitation. Conclusions Enzalutamide treatment achieved only a modest response rate in patients progressing after abiraterone. Although cross-resistance between abiraterone and enzalutamide was a common phenomenon, it was not inevitable, and a small but significant number of patients showed significant benefit from sequential treatment.