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Targeted Oncology

, Volume 13, Issue 4, pp 495–500 | Cite as

Targeted Next-Generation Sequencing in Men with Metastatic Prostate Cancer: a Pilot Study

  • Pedro C. Barata
  • Prateek Mendiratta
  • Brandie Heald
  • Stefan Klek
  • Petros Grivas
  • Davendra P. S. Sohal
  • Jorge A. Garcia
Short Communication

Abstract

Introduction

Tumor profiling by targeted next-generation sequencing (tNGS) and personalized treatment based on these results is becoming increasingly common in patients with metastatic solid tumors, but it remains unclear whether this strategy results in benefit to patients with metastatic prostate cancer (mPCa).

Objective

To assess the clinical utility of tNGS in treatment decision-making for patients with mPCa.

Patients and Methods

Patients with available genomic profiling using tumor tissue (FoundationOne, F1) or cell-free DNA (FoundationACT, Guardant360) were included. Targetable genomic alterations (tGA) included a change in the copy number or mutations in DNA repair genes, mismatch repair genes, PTEN, cyclin-dependent kinases, ERBB2, BRAF, TSC, and the PIK3/mTOR pathway.

Results

The study included 66 patients, 86% of which had metastatic castration-resistant prostate cancer (mCRPC), and who had received a median of 3 (range 0–7) treatments prior to tNGS. The most frequent alterations were found in TP53 (42%), PTEN (35%), androgen receptor (AR) (30%), DNA repair (30%), PIK3CA signaling pathway (21%), cyclin-dependent kinases (15%), BRAF (9%), and MMR/MSI (6%) genes. Among the 45 (68%) tGA+ patients, tNGS influenced treatment in 13 (29%) [PARP inhibitor (n = 7), mTOR inhibitor (n = 4), anti-PD-1 (n = 2), anti-HER2 (n = 1)]. The median progression-free survival (PFS) was 4.1 months [95% confidence interval (CI), 2.8–5.4]. Among tGA+ patients who did not receive tNGS-based therapy, systemic treatment (n = 17) included chemotherapy (71%), new generation anti-androgen therapy (24%), and cabozantinib (6%); the median PFS was 4.3 months (95% CI, 2.6–6.0; p = 0.7 for tGA+ with personalized therapy vs. tGA+ without personalized therapy).

Conclusion

In this cohort, the use of tNGS was feasible, detected frequent genomic alterations, and was used late in the disease course. Further studies and larger portfolios of targeted therapy trials are needed to maximize the benefit of tNGS in this population.

Notes

Compliance with Ethical Standards

Funding

No external funding was used in the preparation of this manuscript.

Conflict of Interest

Brandie Heald has disclosed to be on an advisory board for Invitae and the speakers’ bureau for Myriad Genetics Laboratory. Dr. Petros Grivas has disclosed to be a consultant or advisor for Foundation Medicine, Genentech, Dendreon, Bayer, Driver Inc., Exelixis, Merck & Co., Bristol-Myers Squibb, AstraZeneca, Biocept, Clovis Oncology, EMD Serono, and Seattle Genetics; has received research funding from Mirati Therapeutics, Genentech/Roche, Merck, Oncogenex, Bayer, Pfizer, and AstraZeneca. Dr. Davendra Sohal has disclosed to be a consultant or advisor for Perthera and Foundation Medicine, and received research funding from Novartis, Celgene, OncoMed, Bayer, and Genentech/Roche. Dr. Jorge Garcia has disclosed to be a consultant or advisor for Sanofi, Pfizer, Bayer, Eisai, Exelexis, Medivation/Astellas, and Genentech/Roche; has received research funding from Pfizer, Astellas Pharma, Orion Pharma GmbH, Bayer, Janssen Oncology, Genentech/Roche, and Lilly. Pedro C. Barata, Prateek Mendiratta, and Stefan Klek declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Pedro C. Barata
    • 1
  • Prateek Mendiratta
    • 1
  • Brandie Heald
    • 2
  • Stefan Klek
    • 1
  • Petros Grivas
    • 1
  • Davendra P. S. Sohal
    • 1
  • Jorge A. Garcia
    • 1
    • 3
  1. 1.Taussig Cancer InstituteCleveland ClinicClevelandUSA
  2. 2.Genomic Medicine InstituteCleveland ClinicClevelandUSA
  3. 3.Case Comprehensive Cancer CenterCleveland Clinic—Taussig Cancer InstituteClevelandUSA

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