Clinical variables associated with PSA response to abiraterone acetate in patients with metastatic castration-resistant prostate cancer.
BACKGROUND
Abiraterone acetate (abiraterone) prolongs overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC). This study's objective was to retrospectively identify factors associated with prostate-specific antigen (PSA) response to abiraterone and validate them in an independent cohort. We hypothesized that the neutrophil/lymphocyte ratio (NLR), thought to be an indirect manifestation of tumor-promoting inflammation, may be associated with response to abiraterone.


METHODS
All patients receiving abiraterone at the Princess Margaret (PM) Cancer Centre up to March 2013 were reviewed. The primary end point was confirmed PSA response defined as PSA decline ≥50% below baseline maintained for ≥3 weeks. Potential factors associated with PSA response were analyzed using univariate and multivariable analyses to generate a score, which was then evaluated in an independent cohort from Royal Marsden (RM) NHS foundation.


RESULTS
A confirmed PSA response was observed in 44 out of 108 assessable patients (41%, 95% confidence interval 31%-50%). In univariate analysis, lower pre-abiraterone baseline levels of lactate dehydrogenase, an NLR ≤ 5 and restricted metastatic spread to either bone or lymph nodes were each associated with PSA response. In multivariable analysis, only low NLR and restricted metastatic spread remained statistically significant. A score derived as the sum of these two categorical variables was associated with response to abiraterone (P = 0.007). Logistic regression analysis on an independent validation cohort of 245 patients verified that this score was associated with response to abiraterone (P = 0.003). It was also associated with OS in an exploratory analysis.


CONCLUSIONS
A composite score of baseline NLR and extent of metastatic spread is associated with PSA response to abiraterone and OS. Our data may help understand the role of systemic inflammation in mCRPC and warrant further research.
Departments of Medical Oncology and Haematology.
R
R
Leibowitz-Amit
Departments of Medical Oncology and Haematology.
A J
AJ
Templeton
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
A
A
Omlin
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
C
C
Pezaro
Biostatistics, Princess Margaret Cancer Centre, Toronto, Canada.
E G
EG
Atenafu
Genitourinary Oncology Service, Meir Medical Center, Kfar-Saba, Israel.
D
D
Keizman
Departments of Medical Oncology and Haematology.
F
F
Vera-Badillo
Departments of Medical Oncology and Haematology.
J-A
JA
Seah
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
G
G
Attard
Departments of Medical Oncology and Haematology.
J J
JJ
Knox
Departments of Medical Oncology and Haematology.
S S
SS
Sridhar
Departments of Medical Oncology and Haematology.
I F
IF
Tannock
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
J S
JS
de Bono
Departments of Medical Oncology and Haematology. Electronic address: anthony.joshua@uhn.ca.
A M
AM
Joshua
D000069501:Abiraterone Acetate; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000730:Androstadienes / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009504:Neutrophils / Q000276:immunology*; D011241:Prednisone / Q000627:therapeutic use; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D012189:Retrospective Studies; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
D000726:Androgen Antagonists; D000730:Androstadienes; D014408:Biomarkers, Tumor; D007770:L-Lactate Dehydrogenase; D013254:Steroid 17-alpha-Hydroxylase; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D000069501:Abiraterone Acetate; D011241:Prednisone
NLR; abiraterone acetate; mCRPC; prostate cancer; response