Gene fusions resulting in androgen receptor–modulated ERG gene overexpression can be found in up to 70% of patients with metastatic castration-resistant prostate cancer. In a study reported in Clinical Cancer Research, Attard and colleagues assessed the effect of ERG rearrangement on outcomes in the phase III COU-AA-302 trial comparing abiraterone (Zytiga) and prednisone vs prednisone in chemotherapy-naive patients with metastatic disease.
ERG status was identified for 348 of 1,088 patients in the trial, with ERG rearrangement in 121 (35%). Patients with ERG fusion secondary to deletion of 21q22 and increased copy number of fusion sequences (class 2+ Edel) had significantly longer radiographic progression-free survival after receiving abiraterone and prednisone (22 vs 5.4 months, hazard ratio [HR] = 0.31, P = .0033).
The combination of abiraterone and prednisone was also associated with a significant improvement among patients with no ERG fusion (16.7 vs 8.3 months, HR = 0.53, P = .0002) or other types of ERG rearrangement, although the magnitude of improvement was not as large.
The investigators concluded: “Both ERG-rearranged and wild-type cancers had a significant improvement in [radiographic progression-free survival] with abiraterone and prednisone in the COU-AA-302 trial. However, our data suggest that 2+ Edel cancers, accounting for 15% of all patients with a confirmed ERG status and previously associated with a worse outcome, derived the greatest benefit.” ■
Attard G, et al: Clin Cancer Res 21:1621-1627, 2015.