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


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 70years, range: 54-85years). 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.


CONCLUSIONS
Our preliminary case series data suggest limited activity of enzalutamide in the post-docetaxel and post-abiraterone patient population.
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, Downs Road, Sutton, Surrey, UK.
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Bianchini
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, Downs Road, Sutton, Surrey, UK.
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D
Lorente
Guy's and St. Thomas' NHS Foundation Trust, Great Maze Pond, London, UK.
A
A
Rodriguez-Vida
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, Downs Road, Sutton, Surrey, UK.
A
A
Omlin
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, Downs Road, Sutton, Surrey, UK.
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C
Pezaro
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, Downs Road, Sutton, Surrey, UK.
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R
Ferraldeschi
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, Downs Road, Sutton, Surrey, UK.
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A
Zivi
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, Downs Road, Sutton, Surrey, UK.
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G
Attard
Guy's and St. Thomas' NHS Foundation Trust, Great Maze Pond, London, UK.
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S
Chowdhury
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, Downs Road, Sutton, Surrey, UK. Electronic address: johann.de-bono@icr.ac.uk.
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JS
de Bono
D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes; D000737:Androstenols / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017430:Prostate-Specific Antigen / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism; D012189:Retrospective Studies; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000736:Androstenes; D000737:Androstenols; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide; D017430:Prostate-Specific Antigen; C089740:abiraterone
Abiraterone; Androgen receptor targeting; Castration resistant prostate cancer; Enzalutamide; Hormone therapy