BACKGROUND: 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. PATIENTS AND METHODS: We retrospectively evaluated activity of docetaxel in mCRPC patients previously treated with abiraterone, using Prostate Cancer Working Group and radiological criteria. RESULTS: 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. CONCLUSION: The activity of docetaxel post-abiraterone appears lower than anticipated and no responses to docetaxel were observed in abiraterone-refractory patients.
BACKGROUND: 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. PATIENTS AND METHODS: We retrospectively evaluated activity of docetaxel in mCRPC patients previously treated with abiraterone, using Prostate Cancer Working Group and radiological criteria. RESULTS: 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. CONCLUSION: The activity of docetaxel post-abiraterone appears lower than anticipated and no responses to docetaxel were observed in abiraterone-refractory patients.
Authors: Emmanuel S Antonarakis; Scott T Tagawa; Giuseppe Galletti; Daniel Worroll; Karla Ballman; Marie Vanhuyse; Guru Sonpavde; Scott North; Costantine Albany; Che-Kai Tsao; John Stewart; Atef Zaher; Ted Szatrowski; Wei Zhou; Ada Gjyrezi; Shinsuke Tasaki; Luigi Portella; Yang Bai; Timothy B Lannin; Shalu Suri; Conor N Gruber; Erica D Pratt; Brian J Kirby; Mario A Eisenberger; David M Nanus; Fred Saad; Paraskevi Giannakakou Journal: J Clin Oncol Date: 2017-06-20 Impact factor: 44.544
Authors: Maria Thadani-Mulero; Luigi Portella; Shihua Sun; Matthew Sung; Alexandre Matov; Robert L Vessella; Eva Corey; David M Nanus; Stephen R Plymate; Paraskevi Giannakakou Journal: Cancer Res Date: 2014-02-20 Impact factor: 12.701