A pilot study utilizing multi-omic molecular profiling to find potential targets and select individualized treatments for patients with previously treated metastatic breast cancer

Gayle S. Jameson*, Emanuel F. Petricoin, Jasgit Sachdev, Lance A. Liotta, David M. Loesch, Stephen P. Anthony, Manpreet K. Chadha, Julia D. Wulfkuhle, Rosa I. Gallagher, Kimberley A. Reeder, Mariaelena Pierobon, Monica R. Fulk, Nina A. Cantafio, Bryant Dunetz, William D. Mikrut, Daniel D. Von Hoff, Nicholas J. Robert

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

The primary objective was to determine if multi-omic molecular profiling (MMP) informed selection of approved cancer treatments could change the clinical course of disease for patients with previously treated metastatic breast cancer (MBC) (i.e., produce a growth modulation index (GMI) ≥1.3). GMI was calculated as the ratio of progression free survival on MMP-selected therapy/time to progression on last prior treatment. To meet the primary objective at least 35 % of the subjects should demonstrate a GMI ≥1.3. Secondary endpoints included determining the response rate (according to RECIST 1.1), the percent of patients with non-progression at 4 months, and overall survival in patients whose therapy is selected by molecular profiling and proteomic analysis. Eligible patients had MBC, with ≥3 prior lines of therapy. A multi-omic based approach was performed incorporating multiplexed immunohistochemistry, c-DNA microarray, and phosphoprotein pathway activation mapping by reverse phase protein array. MMP was performed on fresh core biopsies; results were generated and sent to a Treatment Selection Committee (TSC) for review and treatment selection. Three sites enrolled 28 patients, of which 25 were evaluable. The median range of prior treatment was 7 (range 3–12). The MMP analysis and treatment recommendation were delivered within a median of 15.5 days from biopsy (range 12–23). The TSC selected MMP-rationalized treatment in 100 % (25/25) of cases. None of the MMP-based therapies were the same as what the clinician would have selected if the MMP had not been performed. GMI ≥1.3 was reported in 11/25 (44 %) patients. Partial responses were noted in 5/25 (20 %), stable disease in 8/25 (32 %) and 9/25 (36 %) had no progression at 4 months. This pilot study demonstrates the feasibility of finding possible treatments for patients with previously treated MBC using a multiplexed MMP-rationalized treatment recommendation. This MMP approach merits further investigation.

Original languageEnglish
Pages (from-to)579-588
Number of pages10
JournalBreast Cancer Research and Treatment
Volume147
Issue number3
DOIs
StatePublished - 24 Sep 2014
Externally publishedYes

Keywords

  • Individualized treatment
  • Metastatic breast cancer
  • Molecular profiling
  • Multi-omic profiling
  • Reverse phase protein array (RPPA)
  • Translational oncology
  • Translational research

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