Improvements in radiographic progression-free survival stratified by ERG gene status in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate Journal Article

   

Authors:	Attard, G.; de Bono, J. S.; Logothetis, C. J.; Fizazi, K.; Mukherjee, S. D.; Joshua, A. M.; Schrijvers, D.; Van Den Eertwegh, A. J. M.; Li, W.; Molina, A.; Griffin, T. W.; Kheoh, T.; Ricci, D. S.; Zelinsky, K.; Rathkopf, D. E.; Scher, H. I.; Ryan, C. J.
Article Title:	Improvements in radiographic progression-free survival stratified by ERG gene status in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate
Abstract:	Purpose: Gene fusions leading to androgen receptor-modulated ERG overexpression occur in up to 70% of metastatic castration-resistant prostate cancers (mCRPC). We assessed the association between ERG rearrangement status and clinical benefit from abiraterone acetate. Experimental Design: COU-AA-302 is a phase III trial comparing abiraterone acetate and prednisone versus prednisone in chemotherapy-naïve mCRPC. ERG status was evaluated by FISH on archival tumors. End points included radiographic progression-free survival (rPFS), time to PSA progression (TTPP), rate of ≥50% PSA decline from baseline, and overall survival (OS). Cox regression was used to evaluate association with time-to-event measures and Cochran-Mantel-Haenszel for PSA response. Results: ERG status was defined for 348 of 1,088 intention-to-treat patients. ERG was rearranged in 121 of 348 patients with confirmed ERG status (35%). Cancers with an ERG fusion secondary to deletion of 21q22 and increased copy number of fusion sequences (class 2+ Edel) had a greater improvement in rPFS after abiraterone acetate and prednisone [22 vs. 5.4 months; HR (95% confidence interval, CI), 0.31 (0.15-0.68); P = 0.0033] than cancers with no ERG fusion [16.7 vs. 8.3 months; 0.53 (0.38-0.74); P = 0.0002] or other classes of ERG rearrangement. There was also greater benefit in this subgroup for TTPP. Conclusions: Both ERG-rearranged and wild-type cancers had a significant improvement in rPFS with abiraterone acetate and prednisone in the COU-AA-302 trial. However, our data suggest that 2+ Edel cancers, accounting for 15% of all mCRPC patients and previously associated with a worse outcome, derived the greatest benefit. ©2015 AACR.
Keywords:	adult; cancer chemotherapy; controlled study; human tissue; aged; major clinical study; overall survival; prednisone; outcome assessment; prospective study; prostate specific antigen; progression free survival; genetic association; oncogene; fluorescence in situ hybridization; proportional hazards model; gene rearrangement; gene fusion; abiraterone acetate; chromosome deletion; erg gene; mantel haenszel test; castration resistant prostate cancer; copy number variation; intention to treat analysis; human; male; priority journal; article; chromosome 21q; metastatic castration resistant prostate cancer; radiographic progression free survival; time to psa progression
Journal Title:	Clinical Cancer Research
Volume:	21
Issue:	7
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2015-04-01
Start Page:	1621
End Page:	1627
Language:	English
DOI:	10.1158/1078-0432.ccr-14-1961
PROVIDER:	scopus
PMCID:	PMC4384987
PUBMED:	25593303
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84927587529&partnerID=40&md5=61ad00298131bddc8f8ba939d312dac0
Notes:	Export Date: 4 May 2015 -- Source: Scopus

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