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Table 1 Neoadjuvant trials with trastuzumab-containing regimens which assessed the prognostic values of TILs and immune related gene signatures

From: Interaction of host immunity with HER2-targeted treatment and tumor heterogeneity in HER2-positive breast cancer

Study Treatment N. pts.a Biomarker Tested Outcome Tested Association
CALGB 40601 [100]
NCT00770809
P-H
P-L
P-HL
265 Immune gene signatures [100] pCR IgG signature independently associated with pCR at multivariate analysis
CherLOB [55]
NCT00429299
P-H → FEC-H
P-L → FEC-L
P-HL → FEC-HL
105 TILs [55] pCR Associated with pCR at univariate analyses (no statistical significance beyond PAM50)
EFS Associated with EFS at univariate analyses
86 Immune gene signatures [55] pCR 3 out of 4 signatures maintained association with pCR after correction for PAM50
GeparQuattro [57]
NCT00288002
EC-H → D-H +/−X 178 TILs [57] pCR Associated with pCR at multivariate analysis
GeparQuinto [57]
NCT00567554
EC-H → D-H 162 TILs [57] pCR
EC-L → D-L 158 pCR Not associated with pCR
GeparSixto [38]
NCT01426880
PM-HL +/− C 266 TILs [38] pCR Associated with pCR at multivariate analyses
226 mRNA expression of immunologic genes pCR All 12 immune mRNA markers were associated with pCR (10/12 at multivariate analysis)
NeoALTTO [58]
NCT00553358
P-H
P-L
P-HL
387 TILs [58] pCR Associated with pCR at multivariate analysis
EFS Associated with EFS at multivariate analysis
254 Immune gene signatures [59] pCR two T-cell immune signatures were associated with pCR (only confirmed at multivariate analysis in P-HL arm)
NOAH [75]
ISRCTN86043495
AP → P → CMF 51 Four immune metagenes [45] pCR Not associated with pCR
AP-H → P-H → CMF-H → H 63 pCR 3/4 associated with pCR
NeoSphere [45]
NCT00545688
DH
DPrtz
DHPrtz
HPrtz
243 TILs [45] pCR Not significantly associated with pCR
305 PDL1 by IHC [45] pCR Not significantly associated with pCR
337 Immune genes and metagenes [45] pCR 5 associated with pCR at multivariate analysis (different results in the DHPrtz arm)
Tryphaena [44]
NCT00976989
FEC → DHPrtz
FECHPrtz→DHPrtz
CycloDHPrtz
213 TILs [43] pCR Not significantly associated with pCR
EFS Associated with EFS at multivariate analysis
173 Immune signatures and genes [43] pCR 2 signatures and 4 genes associated with pCR at multivariate analysis
EFS Not associated with EFS at multivariate analysis
PAMELA [9]
NCT01973660
HL 134 TILs at day15 pCR Associated with pCR at multivariate analysis
  1. a Number of patients included in the biomarker analysis
  2. A doxorubicin, C carboplatin, Cyclo cyclophosphamide, CMF cyclophosphamide-methotrexate-fluorouracil, D docetaxel, EC epirubicin-cyclophosphamide, EFS event-free survival, FEC fluorouracil-epirubicin-cyclophosphamide, H trastuzumab, IHC immunohistochemistry, L lapatinib, P paclitaxel, pCR pathologic complete response, PM weekly paclitaxel + non pegylated liposomal doxorubicin, Prtz pertuzumab, TIL tumor infiltrating lymphocytes, X capecitabine
  3. Data from the GeparQuattro trial and from the EC-H→D-H arm of the GeparQuinto trial were analyzed jointly