Does ERG Expression Predict Docetaxel Benefit in Prostate Cancer?

Tumor expression of the oncogene ERG might predict patient benefit from adding docetaxel to androgen deprivation therapy, according to analyses of two phase III clinical trials.

Tumor expression of the oncogene ERG might predict patient benefit from adding docetaxel to androgen deprivation therapy (ADT), according to analyses of data (abstract 5012) from two phase III clinical trials presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago.

ERG-positive status was associated with improved recurrence-free survival (RFS) and progression-free survival (PFS), reported lead author Shanna Rajpar, MD, of the Institut Gustave Roussy in Villejuif, France.

“A high Ki67 index was marginally predictive for RFS benefit related to docetaxel, while PTEN had no predictive effect,” said Rajpar.

Docetaxel plus ADT improves survival among some patients with prostate cancer but biomarkers are needed to identify patients most likely to benefit from this treatment. Because some prostate tumors harbor TMPRSS2-ERG gene fusions that cause ERG overexpression, the study authors sought to analyze the predictive value of pretreatment core biopsy ERG, Ki-67, and PTEN expression in the phase III GETUG 12 and GETUG 15 clinical trials.

Patients with ERG-negative tumors saw no statistically significant difference in PFS when docetaxel was added to ADT, compared to ADT alone (13.2 vs 10.6 months). However, in patients with ERG-positive tumors, adding docetaxel to ADT appeared to improve PFS (10.7 vs 18.8 months).

PTEN expression did not predict treatment outcome (P = .08) and Ki-67 expression was marginally but not statistically significantly associated with RFS (hazard ratio [HR], 0.57; 95% CI, 0.30–1.04; P = .06).

ERG might serve as a better selection criterion for patients undergoing docetaxel treatment but ERG expression in the analysis was limited because tissue was available from few patients in GETUG 15, the team cautioned. In the GETUG 12 study, ERG expression correlated moderately with docetaxel treatment (8-year RFS for ERG-positive disease: 48.6% for ADT alone vs 68.5% with docetaxel; HR, 0.55; 95% CI, 0.29–1.03; P = .059).

The team plans to follow-up with an effort to validate the predictive value of ERG expression for docetaxel activity in metastatic castration-resistant prostate cancer.