19P - The prognostic value of soluble CD73 in advanced triple-negative breast cancer: an exploratory analysis of the SYNERGY trial

Background

Overexpression of CD73 in breast cancer is associated with immunosuppressive, pro-angiogenic tumor microenvironment and with poor patient clinical outcomes. Anti-CD73 antibodies are being investigated in combination with immune checkpoint inhibitors in clinical trials. Here, we investigated the prognostic value of the soluble form of CD73 (sCD73) in patients with advanced triple negative breast cancer (TNBC) treated with first-line durvalumab and chemotherapy, with or without anti-CD73 antibody oleclumab in the randomized, phase II SYNERGY trial (NCT03616886).

Methods

sCD73 levels were measured by ELISA in baseline plasma of 124 patients included in SYNERGY and in 24 healthy donors (HD). We explored association between sCD73 levels and baseline clinical characteristics, treatment response, and survival. Tumor-infiltrating lymphocytes (TILs) were assessed on H&E staining; PD-L1 was analyzed using immunohistochemistry.

Results

TNBC patients had significantly higher baseline sCD73 levels than HD (Mann-Whitney, p<0.001). High baseline levels of sCD73 were associated with liver metastases, high neutrophil-to-lymphocyte ratio (>5), and elevated CA 15-3 at baseline. sCD73 levels showed no association with clinical benefit at 24 weeks or with progression-free survival (PFS). Median overall survival (OS) was significantly shorter in patients with high baseline sCD73 levels compared to those with low sCD73 (18.8 vs. 26.4 months; log-rank, p=0.03). Higher TILs levels correlated with better PFS (log-rank, p=0.04) and OS (log-rank, p=0.03). High PD-L1 expression correlated with better PFS (log-rank, p=0.004). No association was observed between sCD73 levels and TILs or PD-L1 expression. Multivariate analysis (including treatment arm, TILs, PD-L1, sCD73 and disease presentation) confirmed the independent prognostic value of sCD73 (OS; HR=0.5; p=0.02).

Conclusions

In our analysis high baseline sCD73 levels were associated with negative prognostic clinical factors at baseline and with worse OS. The role of sCD73 as independent prognostic factor requires external validation.

Clinical trial identification

NCT03616886; August 6, 2018.

Legal entity responsible for the study

Institut Jules Bordet.

Funding

Institutional grant from AstraZeneca for the clinical trial. Translational analyses were funded by the Association Jules Bordet and the Fondation contre le Cancer (Belgium).

Disclosure

E. Agostinetto: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy fee/honoraria: Eli Lilly , Sandoz, AstraZeneca; Financial Interests, Institutional, Research Grant: Gilead; Financial Interests, Personal, Other, Support to attend medical conferences (travel/accommodation/expenses): Novartis, Eli Lilly, Genetic, Istituto Gentili, Daiichi Sankyo. J. Stagg: Financial Interests, Personal, Advisory Board: Surface Oncology, Tarus Therapeutics, Domain Therapeutics, Iteos Therapeutics; Financial Interests, Personal, Stocks/Shares: Surface Oncology; Financial Interests, Institutional, Research Grant: Surface Oncology, Domain Therapeutics. C. Sotiriou: Financial Interests, Institutional, Advisory Board: Astellas, Vertex, Seattle Genetics, Amgen, INC, Merck & Co; Financial Interests, Personal, Advisory Board: Cepheid, Puma; Financial Interests, Personal, Invited Speaker: Eisai, Prime oncology, Teva; Financial Interests, Institutional, Other, Travel: Roche; Financial Interests, Institutional, Other, Internal speaker: Genentech; Financial Interests, Personal, Other, Regional speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Exact Sciences. L. Buisseret: Financial Interests, Institutional, Advisory Board: Domain Therapeutics; Financial Interests, Institutional, Other, Steering Committee: iTEOS Therapeutics; Financial Interests, Personal, Other, writing of clinical cases: Mirrors of Medicine; Financial Interests, Institutional, Other, Travel grant: Gilead; Financial Interests, Institutional, Research Grant, Research Grant for an investigator initiated trial: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: iTeos Therapeutics; Non-Financial Interests, Personal, Member: EORTC, BSMO. All other authors have declared no conflicts of interest.