Docetaxel Treatment in PTEN- and ERG-aberrant Metastatic Prostate Cancers

Abstract

Loss of PTEN is a common genomic aberration in castration-resistant prostate cancer (CRPC) and is frequently concurrent with ERG rearrangements, causing resistance to next-generation hormonal treatment (NGHT) including abiraterone. The relationship between PTEN loss and docetaxel sensitivity remains uncertain. To study the antitumor activity of docetaxel in metastatic CRPC in relation to PTEN and ERG aberrations. Single-centre, retrospective analysis of PTEN loss and ERG expression using a previously described immunohistochemistry (IHC) binary classification system. Patients received docetaxel between January 1, 2006 and July 31, 2016. Response correlations were analyzed using Pearson's χ2 tests and independent-sample t tests. Overall (OS) and progression-free survival (PFS) were analyzed using univariate and multivariate (MVA) Cox regression and Kaplan-Meier methods. Overall, 215 patients were eligible. Established metastatic CRPC prognostic factors were well balanced between PTEN loss (39%) and normal patients (61%). PTEN loss was associated with shorter median OS (25.4 vs 34.7 mo; hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.18–2.13; p = 0.001). There were no differences in median PFS (8.0 vs 9.1 mo; univariate HR 1.20, 95% CI 0.86–1.68; p = 0.28) and PSA response (53.4% vs 50.6%; p = 0.74). PTEN loss was an independent prognostics factor in MVA. ERG status was available for 100 patients. ERG positivity was not associated with OS or PFS. Limitations include the retrospective nature and the single-centre analysis. Our findings suggest that metastatic CRPC with PTEN loss might benefit more from docetaxel than from NGHT. In this study we found that metastatic prostate cancer with loss of the PTEN switch may benefit more from docetaxel than from abiraterone.