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. 2026;51(7):103329. 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