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

StudyTreatmentN. pts.aBiomarker TestedOutcome TestedAssociation
CALGB 40601 [100]NCT00770809P-HP-LP-HL265Immune gene signatures [100]pCRIgG signature independently associated with pCR at multivariate analysis
CherLOB [55]NCT00429299P-H → FEC-HP-L → FEC-LP-HL → FEC-HL105TILs [55]pCRAssociated with pCR at univariate analyses (no statistical significance beyond PAM50)
EFSAssociated with EFS at univariate analyses
86Immune gene signatures [55]pCR3 out of 4 signatures maintained association with pCR after correction for PAM50
GeparQuattro [57]NCT00288002EC-H → D-H +/−X178TILs [57]pCRAssociated with pCR at multivariate analysis
GeparQuinto [57]NCT00567554EC-H → D-H162TILs [57]pCR
EC-L → D-L158pCRNot associated with pCR
GeparSixto [38]NCT01426880PM-HL +/− C266TILs [38]pCRAssociated with pCR at multivariate analyses
226mRNA expression of immunologic genespCRAll 12 immune mRNA markers were associated with pCR (10/12 at multivariate analysis)
NeoALTTO [58]NCT00553358P-HP-LP-HL387TILs [58]pCRAssociated with pCR at multivariate analysis
EFSAssociated with EFS at multivariate analysis
254Immune gene signatures [59]pCRtwo T-cell immune signatures were associated with pCR (only confirmed at multivariate analysis in P-HL arm)
NOAH [75]ISRCTN86043495AP → P → CMF51Four immune metagenes [45]pCRNot associated with pCR
AP-H → P-H → CMF-H → H63pCR3/4 associated with pCR
NeoSphere [45]NCT00545688DHDPrtzDHPrtzHPrtz243TILs [45]pCRNot significantly associated with pCR
305PDL1 by IHC [45]pCRNot significantly associated with pCR
337Immune genes and metagenes [45]pCR5 associated with pCR at multivariate analysis (different results in the DHPrtz arm)
Tryphaena [44]NCT00976989FEC → DHPrtzFECHPrtz→DHPrtzCycloDHPrtz213TILs [43]pCRNot significantly associated with pCR
EFSAssociated with EFS at multivariate analysis
173Immune signatures and genes [43]pCR2 signatures and 4 genes associated with pCR at multivariate analysis
EFSNot associated with EFS at multivariate analysis
PAMELA [9]NCT01973660HL134TILs at day15pCRAssociated with pCR at multivariate analysis

a Number of patients included in the biomarker analysis

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

Data from the GeparQuattro trial and from the EC-H→D-H arm of the GeparQuinto trial were analyzed jointly