Academic Journal
Circulating Tumor Cell Dynamics after CDK4/6 Inhibitor for Hormone Receptor-Positive Metastatic Breast Cancer: A Biomarker Analysis from the PACE Phase II Study.
| Τίτλος: | Circulating Tumor Cell Dynamics after CDK4/6 Inhibitor for Hormone Receptor-Positive Metastatic Breast Cancer: A Biomarker Analysis from the PACE Phase II Study. |
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| Συγγραφείς: | Gerratana L; Department of Medicine, University of Udine, Udine, Italy.; Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy., Reduzzi C; Department of Medical Oncology, Weill Cornell Medicine, New York, New York.; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Ren Y; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Jeselsohn R; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Mahtani RL; Department of Medical Oncology, Miami Cancer Institute, Miami, Florida., Ma CX; Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri., DeMichele A; Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania., Meisel JL; Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia., Miller K; Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana., Abdou Y; Department of Medicine, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina., Riley EC; Department of Medicine, Brown Cancer Center, University of Louisville Health, Louisville, Kentucky., Qamar R; Aurora Cancer Care, Milwaukee, Wisconsin., Sharma P; Department of Medical Oncology, University of Kansas Medical Center, Westwood, Kansas., Reid SA; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee., Ko N; Department of Medical Oncology, Boston Medical Center, Boston, Massachusetts., Liu Y; Pfizer, La Jolla, California., Gauthier E; Pfizer, La Jolla, California., Burstein HJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., DeMeo M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Tolaney SM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Regan MM; Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts., Cristofanilli M; Department of Medical Oncology, Weill Cornell Medicine, New York, New York.; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Mayer EL; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts. |
| Πηγή: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2025 Nov 03; Vol. 31 (21), pp. 4510-4517. |
| Τύπος έκδοσης: | Journal Article; Clinical Trial, Phase II; Randomized Controlled Trial; Multicenter Study |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Denville, NJ : American Association for Cancer Research, c1995- |
| Ιατρικοί όροι (MeSH): | Neoplastic Cells, Circulating*/pathology , Neoplastic Cells, Circulating*/drug effects , Neoplastic Cells, Circulating*/metabolism , Breast Neoplasms*/drug therapy , Breast Neoplasms*/pathology , Breast Neoplasms*/blood , Breast Neoplasms*/mortality , Breast Neoplasms*/genetics , Breast Neoplasms*/metabolism , Cyclin-Dependent Kinase 4*/antagonists & inhibitors , Biomarkers, Tumor*/blood , Cyclin-Dependent Kinase 6*/antagonists & inhibitors , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use , Antineoplastic Combined Chemotherapy Protocols*/adverse effects, Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Erb-b2 Receptor Tyrosine Kinases/metabolism ; Fulvestrant/administration & dosage ; Protein Kinase Inhibitors/administration & dosage ; Protein Kinase Inhibitors/therapeutic use ; Pyridines/administration & dosage ; Humans ; Female ; Middle Aged ; Prognosis ; Aged ; Adult ; Neoplasm Metastasis ; Piperazines |
| Περίληψη: | Purpose: Circulating tumor cells (CTC) 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 patients with HR+/HER2- MBC experiencing progression on aromatase inhibitors 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 stage IVindolent or stage IVaggressive. Concurrent ctDNA analysis was performed using Guardant360. Progression-free survival (PFS) was the primary endpoint. Results: Among 220 randomly assigned patients, 203 were evaluable for baseline CTCs; 76% had detectable CTCs and 49% were stage IVaggressive. Patients with de novo MBC were more frequently stage IVaggressive (47.5% vs. 30.8%). Baseline CTCs were prognostic with median PFS of 5.7 months for stage IVindolent and 3.5 months for stage IVaggressive patients [HR = 1.69; 90% confidence interval (CI), 1.27-2.24; P < 0.001]. In stage IVaggressive patients, F + P and F + P + A improved PFS versus fulvestrant 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 stage IVindolent patients (interaction P = 0.0148 and P = 0.0033, respectively). Conclusions: Baseline CTC enumeration provides significant prognostic information in HR+/HER2- MBC. Stage IVaggressive patients derive greater benefit from F + P or F + P + A over fulvestrant alone, independent of clinical or ctDNA features. This highlights the potential of CTCs to guide treatment decision-making. (©2025 American Association for Cancer Research.) |
| Grant Information: | Dana-Farber Cancer Institute (DFCI) |
| Substance Nomenclature: | EC 2.7.11.22 (Cyclin-Dependent Kinase 4) 0 (Biomarkers, Tumor) 0 (Receptors, Estrogen) EC 2.7.11.22 (Cyclin-Dependent Kinase 6) 0 (Receptors, Progesterone) EC 2.7.10.1 (Erb-b2 Receptor Tyrosine Kinases) 22X328QOC4 (Fulvestrant) 0 (Protein Kinase Inhibitors) 0 (Pyridines) 0 (Piperazines) EC 2.7.11.22 (CDK4 protein, human) G9ZF61LE7G (palbociclib) EC 2.7.11.22 (CDK6 protein, human) |
| Entry Date(s): | Date Created: 20250825 Date Completed: 20251103 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| DOI: | 10.1158/1078-0432.CCR-25-0327 |
| PMID: | 40853871 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-25-0327 |