title: A pilot study utilizing multi-omic molecular profiling to find potential targets and select individualized treatments for patients with previously treated metastatic breast cancer.
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.
authors.affiliation: Virginia G Piper Cancer Center - Clinical Trials, Scottsdale Healthcare, Scottsdale, AZ, USA, GJameson@SHC.org.
authors.forename: Gayle S
authors.initials: GS
authors.lastname: Jameson
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: Jasgit
authors.initials: J
authors.lastname: Sachdev
authors.forename: Lance A
authors.initials: LA
authors.lastname: Liotta
authors.forename: David M
authors.initials: DM
authors.lastname: Loesch
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Anthony
authors.forename: Manpreet K
authors.initials: MK
authors.lastname: Chadha
authors.forename: Julia D
authors.initials: JD
authors.lastname: Wulfkuhle
authors.forename: Rosa I
authors.initials: RI
authors.lastname: Gallagher
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Reeder
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Pierobon
authors.forename: Monica R
authors.initials: MR
authors.lastname: Fulk
authors.forename: Nina A
authors.initials: NA
authors.lastname: Cantafio
authors.forename: Bryant
authors.initials: B
authors.lastname: Dunetz
authors.forename: William D
authors.initials: WD
authors.lastname: Mikrut
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Robert
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001706:Biopsy; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D057285:Precision Medicine / Q000379:methods*; D016896:Treatment Outcome