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

Rescigno P1,2, Lorente D3, Dolling D1, Ferraldeschi R1, Rodrigues DN1, Riisnaes R1, Miranda S1, Bianchini D1, Zafeiriou Z1, Sideris S1, Ferreira A1, Figueiredo I1, Sumanasuriya S1, Mateo J1, Perez-Lopez R1, Sharp A1, Tunariu N1, de Bono JS1.

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Abstract

BACKGROUND:

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.

OBJECTIVE:

To study the antitumor activity of docetaxel in metastatic CRPC in relation to PTEN and ERG aberrations.

DESIGN SETTING AND PARTICIPANTS:

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.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

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.

RESULTS AND LIMITATIONS:

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.