LAUSR

Background: Immune checkpoint blockade by anti-PD-L1 antibody atezolizumab has demonstrated clinical benefits in metastatic triple negative breast cancer (mTNBC). IL-6 and IL-8 myeloid inflammation is linked to poor prognosis in cancer patients treated with chemotherapy, but its association with single agent atezolizumab-treated patients with mTNBC remains unknown. In this study, we investigated the association of biomarkers (BM) of systemic inflammation with clinical outcomes in patients with mTNBC treated with atezolizumab monotherapy. Methods: Baseline pre-treatment plasma samples were collected from mTNBC patients enrolled in the Phase I atezolizumab monotherapy clinical trial PCD4989g (NCT01375842, n = 116). IL-6, IL-8 and CRP were tested by ELISA or Luminex assays and their levels were assessed for association with baseline clinical demographic characteristics and atezolizumab clinical activity for response rate (ORR), progression free (PFS) and overall survival (OS). Results: Baseline IL-6, IL-8, and CRP levels were positively associated with the clinical prognostic traits ECOG performance status (>0), presence of liver metastases, large size of target lesions (>=6.5cm), and increased LDH (>=1.5xULN). Elevated baseline IL-6 and CRP, but not IL-8, were also linked with later lines of therapy (>=2). Univariate analyses showed that IL-6 (>=15pg/ml), IL-8 (>=11.4pg/ml) and CRP (>=3mg/L) were associated with reduced OS and PFS (Table), but only CRP was associated to reduced ORR. Multivariate analyses considering the aforementioned clinical demographic variables showed that IL-6 (HR 2.00 [1.16-3.38]); and CRP (HR 2.74 [1.49-5.28]), but not IL-8 (HR 1.07 [0.78-1.74]), were associated with OS. Conclusion: The systemic IL-6/CRP inflammatory axis is an independent factor linked with poor outcomes of mTNBC patients treated with atezolizumab monotherapy and may play unique roles in affecting the anti-tumor activity in this hard to treat patient population. Citation Format: Yijin Li, Marcella Fasso, Leisha A. Emens, Luciana Molinero. Biomarkers of systemic inflammation associated to reduced clinical activity of atezolizumab monotherapy in patients with metastatic triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT001.