In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 6_suppl ( 2017-02-20), p. 160-160
Abstract:
160 Background: Circulating aberrations (copy number/point mutation] of androgen receptor ( AR) as well as serum chromogranin A (CgA) have been associated to treatment response and clinical outcome in CRPC patients (pts) treated with abiraterone (abi)/enzalutamide(enza). Methods: We determined AR aberrations by digital PCR, Taqman and targeted-next generation sequencing on pre-treatment plasma from 169 CRPC pts treated with abi 1g/od (n = 96) and prednisone 5mg/bid or enza 160mg/od (n = 73) (Romanel, 2015; Salvi, 2015; Salvi, 2016). All pts were subdivided into 3 groups using receiver-operating characteristic (ROC) curves (Burgio, 2014; Conteduca, 2014) to evaluate properly the impact of CgA levels: serum CgA level was normal when 〈 120 ng/ml (group A,n = 76); within 3 times the upper normal value(UNV) when between 120 and 360(group B,n = 57), more than 3 times UNV when 〉 360(group C,n = 36). The primary endpoint was the correlation between AR aberrations and CgA level. The secondary endpoints were progression-free/overall survival (PFS/OS) and PSA response rate (RR) ( 〉 50% PSA decline after 12 weeks of therapy) stratified by AR status and CgA level. Results: We observed AR gain in 57(33.7%) of 169 pts, 29(30.2%) of 96 pts treated with abi and 28(38.3%) of 73 treated with enza. Circulating AR status was independent from baseline CgA levels in all pts (p = 0.36). In only AR-normal pts, we showed a significant survival difference among 3 CgA groups (P 〈 0.0001), particularly Group C vs. A+B [HR (hazard ratio) 5.1, 95%CI (confidence interval) 2.37-10.96 and HR 3.7 95%CI 1.79-7.69, respectively for PFS/OS]. We reported no difference of PFS/OS in AR-gained pts (P = 0.6 and P = 0.1, respectively with HR~0.6 in all CgA groups). In addition, group C vs. A+B had a significant PSA RR [P = 0.03 odds ratio (OR) 2.7 95%CI 1.02-7.30] in AR-normal pts. No PSA RR difference was observed in AR-gained pts (P = 1.0 OR 0.97 95%CI 0.18-5.26). Conclusions: In CRPC pts treated with abi/enza, baseline CgA levels may be an additional predictive/prognostic factor, especially in a particular set of CRPC pts with normal plasma AR status and worse treatment outcome. This association needs a prospective larger study.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.6_suppl.160
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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