Antitumour activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and abiraterone

• Published in: European journal of cancer (1990) 2014-01, Vol.50 (1), p.78-84
• Main Authors: Bianchini, D, Lorente, D, Rodriguez-Vida, A, Omlin, A, Pezaro, C, Ferraldeschi, R, Zivi, A, Attard, G, Chowdhury, S, de Bono, J.S
• Format: Article
• Language: English
• Subjects: Abiraterone; Aged; Aged, 80 and over; Androgen receptor targeting; Androstenes; Androstenols - adverse effects; Androstenols - therapeutic use; Benzamides; Biological and medical sciences; Castration resistant prostate cancer; Docetaxel; Enzalutamide; Hematology, Oncology and Palliative Medicine; Hormone therapy; Humans; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nitriles; Pharmacology. Drug treatments; Phenylthiohydantoin - adverse effects; Phenylthiohydantoin - analogs & derivatives; Phenylthiohydantoin - therapeutic use; Prostate-Specific Antigen - metabolism; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - metabolism; Retrospective Studies; Taxoids - adverse effects; Taxoids - therapeutic use; Treatment Outcome; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2013.08.020

Abstract Background The new generation anti-androgen enzalutamide and the potent CYP17 inhibitor abiraterone have both demonstrated survival benefits in patients with metastatic castration-resistant prostate cancer (CRPC) progressing after docetaxel. Preliminary data on the antitumour activity of abiraterone after enzalutamide have suggested limited activity. The antitumour activity and safety of enzalutamide after abiraterone in metastatic CRPC patients is still unknown. Patients and Methods We retrospectively identified patients treated with docetaxel and abiraterone prior to enzalutamide to investigate the activity and safety of enzalutamide in a more advanced setting. Prostate specific antigen (PSA), radiological and clinical assessments were analysed. Results 39 patients with metastatic CRPC were identified for this analysis (median age 70 years, range: 54–85 years). Overall 16 patients (41%) had a confirmed PSA decline of at least 30%. Confirmed PSA declines of ⩾50% and ⩾90% were achieved in 5/39 (12.8%) and 1/39 (2.5%) respectively. Of the 15 patients who responded to abiraterone, two (13.3%) also had a confirmed ⩾50% PSA decline on subsequent enzalutamide. Among the 22 abiraterone-refractory patients, two (9%) achieved a confirmed ⩾50% PSA decline on enzalutamide. Conclusion Our preliminary case series data suggest limited activity of enzalutamide in the post-docetaxel and post-abiraterone patient population.