Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance?

• Published in: Annals of oncology Vol. 23; no. 11; pp. 2943 - 2947
• Main Authors: Mezynski, J., Pezaro, C., Bianchini, D., Zivi, A., Sandhu, S., Thompson, E., Hunt, J., Sheridan, E., Baikady, B., Sarvadikar, A., Maier, G., Reid, A.H.M., Mulick Cassidy, A., Olmos, D., Attard, G., de Bono, J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-11-2012; Oxford University Press
• Subjects: abiraterone; Aged; Aged, 80 and over; androgen receptor; Androgen Receptor Antagonists - therapeutic use; Androstenes; Androstenols - therapeutic use; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; castration-resistant prostate cancer; Disease Progression; Docetaxel; Drug Interactions; Drug Resistance, Neoplasm; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Prostate-Specific Antigen - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - mortality; Receptors, Androgen - metabolism; response rate; Steroid 17-alpha-Hydroxylase - antagonists & inhibitors; Taxoids - therapeutic use; Testosterone - blood; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; abiraterone; androgen receptor; castration-resistant prostate cancer; docetaxel; response rate; Antineoplastic agent; Urinary system disease; Prostate disease; Abiraterone; Docetaxel; Response rate; Antiandrogen; Antihormone; Malignant tumor; Biological activity; Treatment; Castration; Taxane derivatives; Androgen receptor; Inhibitor; Cross resistance; Antimitotic; Male genital diseases; Prostate cancer; Cancer; Hormonal receptor
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mds119

Abiraterone and docetaxel are both approved treatments for men with metastatic castration-resistant prostate cancer (mCRPC). Abiraterone pre-docetaxel is currently undergoing evaluation in a phase III study. In vitro studies indicate that taxanes may act by disrupting androgen receptor signalling. We hypothesised that prior abiraterone exposure would adversely impact docetaxel efficacy.
We retrospectively evaluated activity of docetaxel in mCRPC patients previously treated with abiraterone, using Prostate Cancer Working Group and radiological criteria.
Of the 54 patients treated with abiraterone, 35 subsequently received docetaxel. Docetaxel resulted in a prostate-specific antigen (PSA) decline of ≥50% in nine patients [26%, 95% confidence interval (CI) 13% to 43%], with a median time to PSA progression of 4.6 months (95% CI 4.2% to 5.9%). PSA declines ≥30% were achieved by 13 patients (37%, 95% CI 22% to 55%). The median overall survival was 12.5 months (95% CI 10.6–19.4). All patients who failed to achieve a PSA fall on abiraterone and were deemed abiraterone-refractory were also docetaxel-refractory (N = 8). In the 24 patients with radiologically evaluable disease, partial responses were reported in four patients (11%), none of whom were abiraterone-refractory.
The activity of docetaxel post-abiraterone appears lower than anticipated and no responses to docetaxel were observed in abiraterone-refractory patients.