Circulating-tumor DNA as predictor of enzalutamide response post-abiraterone treatment in metastatic castration-resistant prostate cancer.

The crossover from abiraterone acetate (AA) to enzalutamide (ENZA) is a frequent approach in clinical practice. Our aim was to explore the role of genomic alterations as putative biomarkers of response to sequential AA followed by ENZA in mCRPC and their association with clinical outcomes.

This was a multi-center, retrospective analysis of mCRPC patients with circulating-tumor DNA (ctDNA) post-AA and prior to ENZA treatment. Objectives of this analysis were to assess PSA response, time to PSA progression (TTP) and overall survival (OS) in mCRPC patients treated with ENZA following progression on AA with respect to genomic aberrations detected by ctDNA.

A total of 28 patients with mCRPC were identified. Median time between AA and ENZA was 3.1 months and median initial PSA prior to ENZA was 35.0 ng/mL. Nine patients (32.1%) achieved PSA responses to ENZA. Most patients (79.0%) achieved confirmed PSA progression with median TTP of 1.6 months (95% CI, 0.7-2.4). Somatic alterations in AR genes were detected in 36.0% of patients with other common alterations detected including 39.0% TP53, 11.0% DNA repair, and 11.0% PTEN. A lack of AR alterations was associated with better PSA response to ENZA (p = 0.04).

While lack of AR alterations in ctDNA was associated with more favorable outcomes, the present dataset is insufficient to recommend the use of ctDNA to impact clinical decision-making in this setting. Further understanding of the implications of the genomic phenotype in ctDNA of castration-resistant tumors and the potential therapeutic implications is required.

Cancer treatment and research communications. 2020 Jul 14 [Epub ahead of print]

Marcus Moses, Alex Niu, Michael B Lilly, Andrew W Hahn, Roberto Nussenzveig, Elisa Ledet, Charlotte Manogue, Patrick Cotogno, Brian Lewis, Jodi Layton, Neeraj Agarwal, Oliver Sartor, Pedro C Barata

Department of Internal Medicine, Section of Hematology and Medical Oncology, Tulane University School of Medicine, 1430 Tulane Ave., New Orleans 70112, LA, USA., Medical University of South Carolina, Charleston, SC, USA., MD Anderson Cancer Center, University of Texas, Houston, TX, USA., Huntsman Cancer Institute, University of Utah, Salt Lake, UT, USA., Department of Internal Medicine, Section of Hematology and Medical Oncology, Tulane University School of Medicine, 1430 Tulane Ave., New Orleans 70112, LA, USA. Electronic address: .