Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate.
OBJECTIVE
The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate, an oral, specific, irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resistant prostate cancer (CRPC).


METHODS
In this multicenter, two-stage, phase II study, abiraterone acetate 1,000 mg was administered once daily continuously. The primary end point was achievement of a prostate-specific antigen (PSA) decline of > or = 50% in at least seven of 35 patients. Per an attained phase II design, more than 35 patients could be enrolled if the primary end point was met. Secondary objectives included: PSA declines of > or = 30% and > or = 90%; rate of RECIST (Response Evaluation Criteria in Solid Tumors) responses and duration on study; time to PSA progression; safety and tolerability; and circulating tumor cell (CTC) enumeration.


RESULTS
Docetaxel-treated patients with CRPC (N = 47) were enrolled. PSA declines of > or = 30%, > or = 50% and > or = 90% were seen in 68% (32 of 47), 51% (24 of 47), and 15% (seven of 47) of patients, respectively. Partial responses (by RECIST) were reported in eight (27%) of 30 patients with measurable disease. Median time to PSA progression was 169 days (95% CI, 113 to 281 days). The median number of weeks on study was 24, and 12 (25.5%) of 47 patients remained on study > or = 48 weeks. CTCs were enumerated in 34 patients; 27 (79%) of 34 patients had at least five CTCs at baseline. Eleven (41%) of 27 patients had a decline from at least five to less than 5 CTCs, and 18 (67%) of 27 had a > or = 30% decline in CTCs after starting treatment with abiraterone acetate. Abiraterone acetate was well tolerated.


CONCLUSIONS
Abiraterone acetate has significant antitumor activity in post-docetaxel patients with CRPC. Randomized, phase III trials of abiraterone acetate are underway to define the future role of this agent.
The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK. johann.de-bono@icr.ac.uk
Alison H M
AH
Reid
Gerhardt
G
Attard
Daniel C
DC
Danila
Nikhil Babu
NB
Oommen
David
D
Olmos
Peter C
PC
Fong
L Rhoda
LR
Molife
Joanne
J
Hunt
Christina
C
Messiou
Christopher
C
Parker
David
D
Dearnaley
Joost F
JF
Swennenhuis
Leon W M M
LW
Terstappen
Gloria
G
Lee
Thian
T
Kheoh
Arturo
A
Molina
Charles J
CJ
Ryan
Eric
E
Small
Howard I
HI
Scher
Johann S
JS
de Bono
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000736:Androstenes; D000737:Androstenols / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000627:therapeutic use
D000726:Androgen Antagonists; D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D013254:Steroid 17-alpha-Hydroxylase; D017430:Prostate-Specific Antigen; C089740:abiraterone