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

Gerhardt Attard, Johann S. De Bono, Christopher J. Logothetis, Karim Fizazi, Som D. Mukherjee, Anthony M. Joshua, Dirk Schrijvers, Alfons J.M. Van Den Eertwegh, Weimin Li, Arturo Molina, Thomas W. Griffin, Thian Kheoh, Deborah S. Ricci, Kathy Zelinsky, Dana E. Rathkopf, Howard I. Scher, Charles J. Ryan

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46 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1621-1627
Number of pages7
JournalClinical Cancer Research
Volume21
Issue number7
DOIs
StatePublished - Apr 1 2015

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