B Lymphocytes Are a Predictive Marker of Eribulin Response and Overall Survival in Locally Advanced or Metastatic Breast Cancer: A Multicenter, Two-Cohort, Non-Randomized, Open-Label, Retrospective Study

Abstract

Triple-negative breast cancer has no specific treatment and unfavorable prognosis. Eribulin is one of the drugs widely used in this cohort of patients. In addition to its antimitotic effect, eribulin has an immunomodulant effect on the tumor microenvironment. In this study, we discover immunological markers, such as tumor-infiltrating lymphocytes, CD8+, CD4+, FoxP3+, CD20+ lymphocytes, and their PD1 positivity or negativity, with the ability to predict benefits from eribulin within locally advanced or metastatic triple-negative breast cancer. The primary objective was to explore the association of composition of immune cells in the microenvironment with response to eribulin. The key secondary objective was overall survival. Seven-color multiplex immunofluorescence was used to phenotype lymphocytes in the primary tumor. It has been shown that the PD1-negative-to-PD1-positive B cells ratio in primary tumors more than 3 is an independent predictor of the short-term effectiveness of eribulin [OR (95%CI) 14.09 (1.29-153.35), p=0.0029] and worse overall survival [HR (95%CI) 11.25 (1.37-70.25), p=0.0009] in patients with locally advanced or metastatic triple-negative breast cancer.

Results of a Phase Ib Study Investigating Durvalumab in Combination with Eribulin in Patients with HER2-Negative Metastatic Breast Cancer and Recurrent Ovarian Cancer

“…Studies looking at combination chemotherapy with immune checkpoint inhibitors in ROC have shown limited benefit and have not been done with eribulin [8]. Eribulin is a chemotherapeutic agent that has been extensively studied as a partner to immunotherapy given its ability to prime the tumor microenvironment for an optimal immunotherapy response [14, 15]. Historically, however, adding pembrolizumab to eribulin did not improve ORR, PFS, or OS in heavily pretreated HR+ MBC patients when compared to eribulin alone [5].…”

“…This remodeling increases tumor microvessel density and improves perfusion, decreasing inner tumor hypoxia which reduces tumor aggressiveness. Eribulin has also been shown to increase the ability of tumor-infiltrating lymphocytes to penetrate tumor implants and increase the effectiveness of immunotherapy-based interventions [15]. ENHANCE-1 was a phase Ib/IIb study evaluating eribulin plus pembrolizumab in patients with metastatic TNBC [16].…”