Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
Circulating Tumor Cell Dynamics after CDK4/6 Inhibitor for Hormone Receptor-Positive Metastatic Breast Cancer: A Biomarker Analysis from the PACE Phase II Study.
СтатьяКлиническое исследование II фазыРандомизированное исследованиеМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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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 Michele, Tolaney Sara M, Regan Meredith M, Cristofanilli Massimo, Mayer Erica L
Аннотация
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.
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.
Предметные рубрики MeSH
HumansNeoplastic Cells, CirculatingFemaleBreast NeoplasmsCyclin-Dependent Kinase 4Biomarkers, TumorReceptors, EstrogenCyclin-Dependent Kinase 6Receptors, ProgesteroneMiddle AgedPrognosisAgedErb-b2 Receptor Tyrosine KinasesAntineoplastic Combined Chemotherapy ProtocolsFulvestrantProtein Kinase InhibitorsAdultNeoplasm MetastasisPyridinesPiperazines