Circulating tumor cells dynamics after CDK4/6 inhibitor for hormone-receptor positive metastatic breast cancer: a biomarker analysis from the PACE phase II study. Academic Article uri icon

Overview

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<0.001). In StageIV aggressive patients, F+P and F+P+A improved PFS versus F alone (HR 0.43, 90% CI 0.25-0.71 and HR 0.26, 90% CI 0.14-0.49, respectively). No benefit was observed in StageIV indolent patients (interaction p=0.0148 and p=0.0033, respectively). 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.

authors

  • Gerratana, Lorenzo
  • Reduzzi, Carolina
  • Ren, Yue
  • Jeselsohn, Rinath
  • Mahtani, Reshma L
  • Ma, Cynthia X
  • DeMichele, Angela
  • Meisel, Jane L
  • Miller, Kathy
  • Abdou, Yara
  • Riley, Elizabeth C
  • Qamar, Rubina
  • Sharma, Priyanka
  • Reid, Sonya A
  • Ko, Naomi
  • Liu, Yuan
  • Gauthier, Eric
  • Burstein, Harold J
  • DeMeo, Michelle
  • Tolaney, Sara M
  • Regan, Meredith M
  • Cristofanilli, Massimo
  • Mayer, Erica L

publication date

  • August 25, 2025

Identity

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-25-0327

PubMed ID

  • 40853871