Response to subsequent docetaxel in a patient cohort with metastatic castration-resistant prostate cancer after abiraterone acetate treatment.
BACKGROUND
Docetaxel or AA are therapeutic options for mCRPC. We retrospectively analyzed clinical outcomes with subsequent docetaxel in patients with mCRPC after disease progression (DP) with AA to evaluate cross resistance between these therapies.


METHODS
Patients with chemotherapy-naive mCRPC who were treated with AA in previously reported phase I to III trials, who had DP, and were subsequently treated (not on study) with docetaxel, were included. Acquired AA resistance was defined as: PSA decline > 50% from baseline or radiographically stable disease for ≥ 8 months, with subsequent DP. All other patients were defined as having primary AA resistance. Efficacy outcomes after docetaxel therapy were analyzed.


RESULTS
We identified 23 patients who were treated with docetaxel after DP with AA, including 14 (61%) with acquired and 9 (39%) with primary AA resistance. Median duration between discontinuation of AA and docetaxel initiation was 2.7 months (range, 0.2-14.7 months). Subsequent docetaxel therapy led to ≥ 30% PSA decline in 15 patients (65%) and ≥ 50% PSA decline in 11 patients (48%). Median OS from date of first docetaxel dose was 12.4 months (95% confidence interval, 8.2-19.6). Patients with previous primary versus acquired AA resistance had similar outcomes with subsequent docetaxel therapy.


CONCLUSIONS
In this retrospective analysis, the type of AA resistance did not appear to affect outcomes with subsequent docetaxel. The PSA response rates observed suggest a lack of cross-resistance between docetaxel and AA, but prospective studies are needed to evaluate for potential cross-resistance and optimize sequences of therapy in patients with mCRPC.
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA. Electronic address: Rahul.Aggarwal@ucsf.edu.
Rahul
R
Aggarwal
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.
Anna
A
Harris
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.
Carl
C
Formaker
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.
Eric J
EJ
Small
Janssen Research & Development, Menlo Park, CA.
Arturo
A
Molina
Janssen Research & Development, Los Angeles, CA.
Thomas W
TW
Griffin
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.
Charles J
CJ
Ryan
D000069501:Abiraterone Acetate; D000368:Aged; D000736:Androstenes / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
D000736:Androstenes; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D013254:Steroid 17-alpha-Hydroxylase; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate
Androgen signaling; Chemotherapy; Cross-resistance; PSA response; Subsequent therapy