The following article features coverage from the American Association for Cancer Research (AACR) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

High baseline levels of the inflammatory biomarkers, interleukin-6 and C-reactive protein (CRP), were associated with reduced overall survival (OS) in patients with metastatic triple-negative breast cancer (mTNBC) treated with the programmed cell death ligand 1 (PD-L1) inhibitor, atezolizumab. The findings from this study were presented at the American Association for Cancer Research (AACR) Annual Meeting 2019.

Although high plasma levels of the inflammatory cytokines, interleukin-6 (IL-6) and interleukin-8 (IL-8), and the acute-phase inflammatory protein, C-reactive protein (CRP), have been associated with poor prognosis in patients with cancer treated with chemotherapy, their association with clinical outcomes in patients treated with atezolizumab had not been previously investigated. 

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In this study, enzyme-linked immunosorbent (ELISA) or Luminex assays were used to measure baseline, pretreatment plasma levels of IL-6, IL-8, and CRP collected from 116 patients with metastatic triple-negative breast cancer enrolled in a phase 1 clinical trial of single-agent atezolizumab (ClinicalTrial.gov Identifier: NCT01375842). The levels of these biomarkers were evaluated for their association with clinical characteristics, as well as clinical outcomes, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of these patients. 

Key findings from this study included positive associations between elevated baseline levels of all 3 biomarkers, IL-6 (≥15 pg/mL), IL-8 (≥11.4 pg/mL), and CRP (≥3 mg/L), and the following clinical characteristics: an Eastern Cooperative Oncology Group (ECOG) performance status higher than 0, the presence of liver metastases, target lesion size of at least 6.5 cm, and lactate dehydrogenase levels at 1.5xULN or higher.  Two or more later lines of therapy were associated with high levels of IL-6 and CRP, but not IL-8.

Furthermore, multivariate analyses accounting for these clinical variables, showed associations between shorter OS and elevated levels of IL-6 (hazard ratio [HR], 2.00; 95% CI, 1.16-3.38), and CRP (HR, 2.74; 95% CI, 1.49-5.28), but not IL-8 (HR, 1.07; 95% CI, 0.78-1.74).

Disclosure: The presenters disclosed financial ties to various pharmaceutical companies. For a full list of disclosures, please see the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of AACR 2019 meeting by visiting the conference page.

Reference

  1. Li Y, Fassò M, Emens LA, et al. Biomarkers of systemic inflammation associated to reduced clinical activity of atezolizumab monotherapy in patients with metastatic triple negative breast cancer. Presented at: American Association for Cancer Research (AACR) Annual Meeting 2019; March 29–April 3, 2019; Atlanta, GA. Abstract CTPL01.