Cyclin-Dependent Kinase 4/6 Inhibitors Beyond Progression in Metastatic Breast Cancer: A Retrospective Real-World Biomarker Analysis.

Autor:	Gerratana L; Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy., Davis AA; Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO., Velimirovic M; Massachusetts General Hospital, Boston, MA.; Harvard Medical School, Boston, MA., Reduzzi C; Weill Cornell Medicine, New York, NY., Clifton K; Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO., Bucheit L; Guardant Health, Redwood City, CA., Hensing WL; Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO., Shah AN; Feinberg School of Medicine, Northwestern University, Chicago, IL., Pivetta T; Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy.; Department of Medicine, University of Udine, Udine, Italy., Dai CS; Massachusetts General Hospital, Boston, MA.; Harvard Medical School, Boston, MA., D'Amico P; Feinberg School of Medicine, Northwestern University, Chicago, IL., Wehbe F; Feinberg School of Medicine, Northwestern University, Chicago, IL., Medford A; Massachusetts General Hospital, Boston, MA.; Harvard Medical School, Boston, MA., Wander SA; Massachusetts General Hospital, Boston, MA.; Harvard Medical School, Boston, MA., Gradishar WJ; Feinberg School of Medicine, Northwestern University, Chicago, IL., Behdad A; Feinberg School of Medicine, Northwestern University, Chicago, IL., Ma CX; Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO., Puglisi F; Department of Medical Oncology, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy.; Department of Medicine, University of Udine, Udine, Italy., Bardia A; Massachusetts General Hospital, Boston, MA.; Harvard Medical School, Boston, MA., Cristofanilli M; Weill Cornell Medicine, New York, NY.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2023 May; Vol. 7, pp. e2200531.
DOI:	10.1200/PO.22.00531
Abstrakt:	Purpose: As the continuation beyond progression (BP) of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) is becoming increasingly attractive for the treatment of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), the definition of resistance factors is crucial. The aim of the study was to investigate the impact of CDK 4/6i BP and to explore potential genomic stratification factors. Materials and Methods: We retrospectively analyzed a multi-institutional cohort of patients with HR-positive HER2-negative MBC characterized for circulating tumor DNA through next-generation sequencing before treatment start. Differences across subgroups were analyzed by chi-square test, and survival was tested by univariable and multivariable Cox regression. Further correction was applied by propensity score matching. Results: Among the 214 patients previously exposed to CDK4/6i, 172 were treated with non-CDK4/6i-based treatment (non-CDK) and 42 with CDK4/6i BP. Multivariable analysis showed a significant impact of CDK4/6i BP, TP53 single-nucleotide variants, liver involvement, and treatment line on both progression-free survival (PFS) and overall survival (OS). Propensity score matching confirmed the prognostic role of CDK4/6i BP both for PFS and OS. The favorable impact of CDK4/6i BP was consistent across all subgroups, and a differential benefit was suggested for ESR1 -mutated patients. ESR1 and RB1 mutations were more represented in the CDK4/6i BP subgroup with respect to CDK4/6i upfront. Conclusion: The study highlighted a significant prognostic impact of the CDK4/6i BP strategy with a potential added benefit in patients with ESR1 mutations suggesting the need for an extensive biomarker characterization.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu