Circulating tumor cells dynamics after CDK4/6 inhibitor for hormone-receptor positive metastatic breast cancer: A biomarker analysis from the PACE phase II study

Authors

Lorenzo Gerratana, University of Udine, Udine, Italy.
Carolina Reduzzi, Weill Cornell Medicine, New York, United States.
Yue Ren, Dana-Farber Cancer Institute, Boston, United States.
Rinath Jeselsohn, Dana-Farber Cancer Institute, Boston, MA, United States.
Reshma L. Mahtani, Baptist Health South Florida, United States.
Cynthia X. Ma, Washington University in St. Louis, St, Louis, MO, United States.
Angela DeMichele, University of Pennsylvania School of Medicine, Philadelphia, PA, United States.
Jane L. Meisel, Emory University, Atlanta, GA, United States.
Kathy Miller, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA, Indianapolis, IN, United States.
Yara Abdou, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Elizabeth C. Riley, Brown Cancer Center, University of Louisville Health, United States.
Rubina Qamar, Advocate Health - MidwestFollow
Priyanka Sharma, University of Kansas Medical Center, Westwood, KS, United States.
Sonya A. Reid, Vanderbilt University Medical Center, Nashville, TN, United States.
Naomi Ko, Boston University, Boston, Massachusetts, United States.
Yuan Liu, Pfizer, La Jolla, CA, United States.
Eric Gauthier, Pfizer Inc, San Francisco, CA, United States.
Harold J. Burstein, Dana-Farber Cancer Institute, Boston, MA, United States.
Michelle DeMeo, DFCI, Boston, United States.
Sara M. Tolaney, Dana-Farber Cancer Institute, Boston, Massachusetts, United States.
Meredith M. Regan, Dana-Farber Cancer Institute, Boston, MA, United States.
Massimo Cristofanilli, Weill Cornell Medicine, New York, NY, United States.
Erica L. Mayer, Dana-Farber Cancer Institute, Boston, United States.

Recommended Citation

Gerratana L, Reduzzi C, Ren Y, et al. Circulating Tumor Cell Dynamics after CDK4/6 Inhibitor for Hormone Receptor-Positive Metastatic Breast Cancer: A Biomarker Analysis from the PACE Phase II Study. Clin Cancer Res. 2025;31(21):4510-4517. doi:10.1158/1078-0432.CCR-25-0327

Abstract

Purpose: Circulating tumor cells (CTCs) are biomarkers associated with poor prognosis and treatment resistance in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC). This analysis evaluates the prognostic role of baseline CTC enumeration and its interaction with treatment regimens in patients progressing on CDK4/6 inhibitors.

Experimental design: The PACE trial is a phase II, multicenter, randomized study of HR+/HER2- MBC patients experiencing progression on aromatase inhibitors (AI) and CDK4/6 inhibitors. Patients were randomized 1:2:1 to receive fulvestrant (F), F+palbociclib (F+P), or F+P+avelumab (F+P+A). Baseline CTCs were enumerated using CellSearch™ with a threshold of ≥5 CTCs/7.5 mL to classify patients as StageIV indolent or StageIV aggressive. Concurrent ctDNA analysis was performed using Guardant360®. Progression-free survival (PFS) was the primary endpoint.

Results: Among 220 randomized patients, 203 were evaluable for baseline CTCs; 76% had detectable CTCs, and 49% were StageIV aggressive. Patients with de novo MBC were more frequently StageIV aggressive (47.5% vs. 30.8%). Baseline CTCs were prognostic, with median PFS of 5.7 months for StageIV indolent and 3.5 months for StageIV aggressive patients (HR 1.69, 90% CI 1.27-2.24, P

Conclusions: Baseline CTC enumeration provides significant prognostic information in HR+/HER2- MBC. StageIV aggressive patients derive greater benefit from F+P or F+P+A over F alone, independent of clinical or ctDNA features. This highlights the potential of to guide treatment decision-making.

Type

Article

PubMed ID

40853871