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Investigating potential immune mechanisms of trilaciclib administered prior to chemotherapy in patients with metastatic triple-negative breast cancer.

Authors :
Tan, Antoinette R.
O'Shaughnessy, Joyce
Cao, Subing
Ahn, Sarah
Yi, John S.
Source :
Breast Cancer Research & Treatment; Sep2023, Vol. 201 Issue 2, p307-316, 10p
Publication Year :
2023

Abstract

Purpose: In a phase II trial in patients with metastatic triple-negative breast cancer (mTNBC; NCT02978716), administering trilaciclib prior to gemcitabine plus carboplatin (GCb) enhanced T-cell activation and improved overall survival versus GCb alone. The survival benefit was more pronounced in patients with higher immune-related gene expression. We assessed immune cell subsets and used molecular profiling to further elucidate effects on antitumor immunity. Methods: Patients with mTNBC and ≤ 2 prior chemotherapy regimens for locally recurrent TNBC or mTNBC were randomized 1:1:1 to GCb on days 1 and 8, trilaciclib prior to GCb on days 1 and 8, or trilaciclib alone on days 1 and 8, and prior to GCb on days 2 and 9. Gene expression, immune cell populations, and Tumor Inflammation Signature (TIS) scores were assessed in baseline tumor samples, with flow cytometric analysis and intracellular and surface cytokine staining used to assess immune cell populations and function. Results: After two cycles, the trilaciclib plus GCb group (n = 68) had fewer total T cells and significantly fewer CD8+ T cells and myeloid-derived suppressor cells compared with baseline, with enhanced T-cell effector function versus GCb alone. No significant differences were observed in patients who received GCb alone (n = 34). Of 58 patients in the trilaciclib plus GCb group with antitumor response data, 27 had an objective response. RNA sequencing revealed a trend toward higher baseline TIS scores among responders versus non‑responders. Conclusion: The results suggest that administering trilaciclib prior to GCb may modulate the composition and response of immune cell subsets to TNBC. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01676806
Volume :
201
Issue :
2
Database :
Complementary Index
Journal :
Breast Cancer Research & Treatment
Publication Type :
Academic Journal
Accession number :
165467520
Full Text :
https://doi.org/10.1007/s10549-023-07009-8