Abstract 50P
Background
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.
Methods
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.
Results
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. Table: 50P
50P
| Odds ratio for pCR | 95% CI | p | |
| Univariate | |||
| 7-cytokine score (per 1 unit increase) | 3.04 | 1.22-7.56 | 0.017 |
| Bivariate models | |||
| 7-cytokine score (per 1 unit increase) | 3.34 | 1.001-11.12 | 0.050 |
| TILs (per 1 unit increase) | 0.02 | 1.02-1.32 | 0.020 |
| 7-cytokine score (per 1 unit increase) | 3.46 | 1.06-11.30 | 0.040 |
| TILs ≥ 15% vs <15% | 22.15 | 1.77-276.69 | 0.016 |
| 7-cytokine score (per 1 unit increase) | 3.22 | 1.18-8.76 | 0.022 |
| Basal subtype vs others | 16.36 | 1.54-173.34 | 0.021 |
Conclusions
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.
Clinical trial identification
NCT04659551.
Legal entity responsible for the study
University of Padua - Department of Surgery, Oncology and Gastroenterology.
Funding
Bristol Myers Squibb.
Disclosure
M.V. Dieci: Financial Interests, Personal, Invited Speaker: Eli Lilly, Exact sciences, Gilead, Seagen, Daiichi Sankyo, Novartis; Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, Seagen, Exact Science, Daiichi Sankyo, Gilead; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Personal, Other, Consultancy on educational project: Roche. A. Musolino: Financial Interests, Personal, Advisory Board: Roche, Novartis, Gilead, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Funding: Seagen; Non-Financial Interests, Principal Investigator: Roche, Lilly, Gilead, Novartis. S. Spazzapan: Financial Interests, Personal, Advisory Board: MSD Italia, Seagen, AstraZeneka; Financial Interests, Personal, Invited Speaker: MSD, Novartis, Mundipharma, AstraZeneka, Eli Lilly; Financial Interests, Personal, Other, Congress registration: Pfizer; Financial Interests, Personal, Other, Tutoring: AstraZeneka; Financial Interests, Personal, Other, congress registration and travel expenses: Pfizer; Financial Interests, Personal, Other, Congress registration and travel expenses: Novartis; Financial Interests, Institutional, Invited Speaker: AstraZeneka. G. Griguolo: Financial Interests, Personal, Invited Speaker: Novartis, Eli Lilly; Financial Interests, Personal, Advisory Board: Gilead; Other, Travel Support: Novartis, Amgen, Daiichi Sankyo, Eli Lilly, Gilead; Other, Trave Support: Pfizer. T. Giarratano: Financial Interests, Personal, Other, Congress Honoraria and fees: Roche, Novartis, Seagen, Lilly, Gilead, Daiichi Sankyo, Gentili. F. Miglietta: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Seagen, Pfizer, Lilly, Menarini; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, GSK, AstraZeneca, Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Merck, Exact Sciences, Eisai, Olema Oncology, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano, Pfizer; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.