TY - JOUR
T1 - A pilot study utilizing multi-omic molecular profiling to find potential targets and select individualized treatments for patients with previously treated metastatic breast cancer
AU - Jameson, Gayle S.
AU - Petricoin, Emanuel F.
AU - Sachdev, Jasgit
AU - Liotta, Lance A.
AU - Loesch, David M.
AU - Anthony, Stephen P.
AU - Chadha, Manpreet K.
AU - Wulfkuhle, Julia D.
AU - Gallagher, Rosa I.
AU - Reeder, Kimberley A.
AU - Pierobon, Mariaelena
AU - Fulk, Monica R.
AU - Cantafio, Nina A.
AU - Dunetz, Bryant
AU - Mikrut, William D.
AU - Von Hoff, Daniel D.
AU - Robert, Nicholas J.
N1 - Publisher Copyright:
© 2014, Springer Science+Business Media New York.
PY - 2014/9/24
Y1 - 2014/9/24
N2 - 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.
AB - 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.
KW - Individualized treatment
KW - Metastatic breast cancer
KW - Molecular profiling
KW - Multi-omic profiling
KW - Reverse phase protein array (RPPA)
KW - Translational oncology
KW - Translational research
UR - http://www.scopus.com/inward/record.url?scp=84910651190&partnerID=8YFLogxK
U2 - 10.1007/s10549-014-3117-1
DO - 10.1007/s10549-014-3117-1
M3 - Article
C2 - 25209003
AN - SCOPUS:84910651190
SN - 0167-6806
VL - 147
SP - 579
EP - 588
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -