Neoadjuvant trials with trastuzumab-containing regimens which assessed the prognostic values of TILs and immune related gene signatures
| Study | Treatment | N. pts.a | Biomarker Tested | Outcome Tested | Association |
|---|---|---|---|---|---|
| CALGB 40601 [100]NCT00770809 | P-HP-LP-HL | 265 | Immune gene signatures [100] | pCR | IgG signature independently associated with pCR at multivariate analysis |
| CherLOB [55]NCT00429299 | P-H → FEC-HP-L → FEC-LP-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-HP-LP-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 | DHDPrtzDHPrtzHPrtz | 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 → DHPrtzFECHPrtz→DHPrtzCycloDHPrtz | 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 |
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