Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial.

Autor: Roussos Torres ET; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. evanthia.roussostorres@med.usc.edu.; Department of Medicine, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. evanthia.roussostorres@med.usc.edu., Ho WJ; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Danilova L; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Tandurella JA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Leatherman J; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Rafie C; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.; University of Miami Miller School of Medicine, Miami, FL, USA., Wang C; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Brufsky A; University of Pittsburgh Cancer Institute and UPMC Cancer Center, Pittsburgh, PA, USA., LoRusso P; Yale Cancer Center, New Haven, CT, USA., Chung V; City of Hope, Duarte, CA, USA., Yuan Y; Cedars-Sinai Cancer, Los Angeles, CA, USA., Downs M; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., O'Connor A; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Shin SM; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Hernandez A; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Engle EL; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Piekarz R; Cancer Therapy Evaluation Program (CTEP), National Cancer Institute, Bethesda, MD, USA., Streicher H; Cancer Therapy Evaluation Program (CTEP), National Cancer Institute, Bethesda, MD, USA., Talebi Z; Division of Pharmaceutics and Pharmacology, The Ohio State University, Columbus, OH, USA., Rudek MA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Zhu Q; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Anders RA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Cimino-Mathews A; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Fertig EJ; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Jaffee EM; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Stearns V; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA., Connolly RM; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. roisin.connolly@ucc.ie.; Cancer Research @UCC, College of Medicine and Health, University College Cork, Cork, Ireland. roisin.connolly@ucc.ie.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2024 Jun; Vol. 5 (6), pp. 866-879. Date of Electronic Publication: 2024 Feb 14.
DOI: 10.1038/s43018-024-00729-w
Abstrakt: We report the results of 24 women, 50% (N = 12) with hormone receptor-positive breast cancer and 50% (N = 12) with advanced triple-negative breast cancer, treated with entinostat + nivolumab + ipilimumab from the dose escalation (N = 6) and expansion cohort (N = 18) of ETCTN-9844 ( NCT02453620 ). The primary endpoint was safety. Secondary endpoints were overall response rate, clinical benefit rate, progression-free survival and change in tumor CD8:FoxP3 ratio. There were no dose-limiting toxicities. Among evaluable participants (N = 20), the overall response rate was 25% (N = 5), with 40% (N = 4) in triple-negative breast cancer and 10% (N = 1) in hormone receptor-positive breast cancer. The clinical benefit rate was 40% (N = 8), and progression-free survival at 6 months was 50%. Exploratory analyses revealed that changes in myeloid cells may contribute to responses; however, no correlation was noted between changes in CD8:FoxP3 ratio, PD-L1 status and tumor mutational burden and response. These findings support further investigation of this treatment in a phase II trial.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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