Cyclin-Dependent Kinase 4/6 Inhibitors Beyond Progression in Metastatic Breast Cancer: A Retrospective Real-World Biomarker Analysis.
JCO Precis Oncol
; 7: e2200531, 2023 05.
Article
em En
| MEDLINE
| ID: mdl-37141549
ABSTRACT
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 ANDMETHODS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
DNA Tumoral Circulante
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
JCO Precis Oncol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Itália