scholarly journals Predictive Genomic Biomarkers of Hormonal Therapy Versus Chemotherapy Benefit in Metastatic Castration-resistant Prostate Cancer

Author(s):  
Ryon P. Graf ◽  
Virginia Fisher ◽  
Joaquin Mateo ◽  
Ole V. Gjoerup ◽  
Russell W. Madison ◽  
...  
2015 ◽  
Vol 47 (3) ◽  
pp. 479-484 ◽  
Author(s):  
Su-bo Qian ◽  
Hai-bo Shen ◽  
Qi-feng Cao ◽  
Lin Zhang ◽  
Yi-fan Chen ◽  
...  

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 185-185
Author(s):  
Ugo De Giorgi ◽  
Eleni Efstathiou ◽  
William R. Berry ◽  
Heather Ann Payne ◽  
Katarzyna Madziarska ◽  
...  

185 Background: Men with nonmetastatic castration-resistant prostate cancer (nmCRPC) are at high risk of developing metastatic CRPC. In the primary analysis of PROSPER, enzalutamide (ENZA) provided a statistically significant and clinically meaningful improvement in metastasis-free survival (MFS) in men with nmCRPC. Here we report the impact of prior therapy on MFS. Methods: Eligible men with nmCRPC, prostate-specific antigen (PSA) doubling time ≤ 10 months, and PSA ≥ 2 ng/mL at screening continued androgen deprivation therapy and were randomized 2:1 to ENZA 160 mg or placebo (PBO). The primary endpoint was MFS. Results: 1401 men were enrolled, with a median age of 74 y (range, 50-95 y). In all men, ENZA reduced the risk of metastasis or death by 71% (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.24-0.35; P < .0001). The treatment effect consistently favored ENZA regardless of whether men had prior bilateral orchiectomy, prior radiation, ≤1 or > 1 prior hormonal therapy, or prior bone-targeting therapy (Table). Men who received > 1 prior hormonal therapy had a shorter median MFS than those who received ≤1 line of hormonal therapy (5 months and 3 months in the ENZA and PBO groups, respectively). Conclusions: In men with nmCRPC and rapidly rising PSA, ENZA treatment resulted in a clinically meaningful reduction in the risk of developing metastases or death irrespective of prior surgery, radiation, or bone-targeting therapy. MFS was longer in men who had received ≤1 prior hormonal therapy. Clinical trial information: NCT02003924. [Table: see text]


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 321-321
Author(s):  
Masato Yasui ◽  
Shuko Yoneyama ◽  
Koichi Uemura ◽  
Takashi Kawahara ◽  
Yusuke Hattori ◽  
...  

321 Background: Recently, new androgen pathway inhibitors, abiraterone and enzalutamide, are demonstrated to improve overall survival for metastatic castration-resistant prostate cancer (mCRPC). In Japan, alternative antiandrogen (AA) as second-line hormonal therapy for mCRPC that relapses after initial hormone therapy have been commonly used before new androgen pathway inhibitors. In this study, we attempted to identify the predictive factors for efficacy of AA as second-line hormone therapy. Methods: We identified consecutive 65 mCRPC patients treated with AA as second-line hormonal therapy. All patients were treated with maximum androgen blockade (MAB) initially and evaluated antiandrogen withdrawal syndrome after relapse. We analyzed the correlations between progression-free survival (PFS) of AA and clinicopathological characteristics, including patients’ age, initial PSA levels, PSA levels at flutamide induction, Gleason scores, T stage, N stage, extent of disease (EOD) classifications on bone scan, and the previous duration of prostate cancer sensitivity to MAB. Results: The median duration of prostate cancer sensitivity to MAB was 11.3 months (range: 1.5-53.0 months). In multivariate analysis, four significant risk factors for poor PFS were identified; initial PSA levels ( > 263 ng/mL vs ≤ 263; HR 0.53, p = 0.038), N stage (1 vs 0; HR 3.00, p = 0.001), EOD classifications (3-4 vs 1-2; HR 2.50, p = 0.007), and the previous duration of prostate cancer sensitivity to MAB ( < 12 months vs ≥ 12; HR 2.16, p = 0.026). We stratified the patients into two cohorts with low risk (0-2 risk factor present) and high risk (3-4 risk factors present). We found a significant difference in PFS among risk groups (median PFS 7.3 months vs 1.5, p < 0.000). Conclusions: Initial PSA, N stage, EOD classifications on bone scan, and the previous duration of prostate cancer sensitivity to MAB were the significant predictive factors for efficacy of AA as second-line hormone therapy in patients with mCRPC. These findings might support that decision-making of when to start the new AR pathway inhibitors.


2011 ◽  
Vol 9 (2) ◽  
pp. 95-103 ◽  
Author(s):  
Mari Nakabayashi ◽  
Lillian Werner ◽  
William K. Oh ◽  
Meredith M. Regan ◽  
Philip W. Kantoff ◽  
...  

2017 ◽  
Vol 24 (8) ◽  
pp. 566-572 ◽  
Author(s):  
Atsushi Mizokami ◽  
Yoshifumi Kadono ◽  
Yasuhide Kitagawa ◽  
Kouji Izumi ◽  
Hiroyuki Konaka

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