50P Circulating cytokines to predict pCR to neoadjuvant chemotherapy and nivolumab for ER+/HER2- BC: Analysis of the phase II GIADA trial

Adding an immune checkpoint inhibitor (ICI) to neoadjuvant chemotherapy (NACT) for ER+/HER2- high-risk BC leads to a 24% pCR rate at the cost of irAEs. Biomarkers are needed to improve pts selection. In the GIADA trial, TILs and Basal subtype were independent factors for pCR after chemotherapy and nivolumab (Dieci, CCR 2022). Here we study the association between circulating cytokines and pCR. 43 premenopausal pts with ER+/HER2-, G3 and/or Ki67≥20% BC received neoadjuvant EC (x3) followed by nivolumab (240mg q2w x8) and endocrine therapy. The level of 47 cytokines was measured on plasmacollected at baseline (t0), after EC prior to nivolumab, and at the end of treatment (MILLIPLEX® MAP, Merck Millipore). SAM (q<0.05, ≥2 fold change) was used to identify cytokines associated with pCR. Non parametric test (p<0.05) was used to study the association of cytokines with PAM50 subtype, TILs and immune cells by multiplex IHC on baseline tumor samples. T0 cytokines were evaluable for 38 pts (7 pCR, 31 non-pCR). 7 cytokines were significanlty higher in pCR vs non-pCR pts by SAM (≥2 fold change): IFNγ, GROα, sCD40L, EGF, VEGFA, PDGFAA, and PDGFAABB. Individually, these cytokines were positively associated with intratumoral immune cells including PDL1+ macrophages, PD1+ T cells, as well as granzyme+ CD4+ and CD8+ cells. Only PDGFAABB was positively correlated with TILs, no association with molecular subtype was found. A 7-cytokine score, based on the average level of differentially expressed cytokines in pCR pts, resulted significantly associated with pCR even after correction for TILs or basal subtype (Table). On-treatment cytokine modulation will be presented at the meeting.Table50POdds ratio for pCR95% CIpUnivariate7-cytokine score (per 1 unit increase)3.041.22-7.560.017Bivariate models7-cytokine score (per 1 unit increase)3.341.001-11.120.050TILs (per 1 unit increase)0.021.02-1.320.0207-cytokine score (per 1 unit increase)3.461.06-11.300.040TILs ≥ 15% vs <15%22.151.77-276.690.0167-cytokine score (per 1 unit increase)3.221.18-8.760.022Basal subtype vs others16.361.54-173.340.021 Open table in a new tab We identified a circulating cytokine profile that may predict pCR following NACT+ICI for ER+/HER2- BC. These results, if further validated, may contribute to refine selection of ER+/HER2- BC pts suitable for this strategy.