1. CDK4/6 Inhibitor Efficacy in ESR1 -Mutant Metastatic Breast Cancer.
- Author
-
Lloyd MR, Brett JO, Carmeli A, Weipert CM, Zhang N, Yu J, Bucheit L, Medford AJ, Wagle N, Bardia A, and Wander SA
- Subjects
- Humans, Female, Middle Aged, Aged, Adult, Aromatase Inhibitors therapeutic use, Piperazines therapeutic use, Neoplasm Metastasis, Fulvestrant therapeutic use, Protein Kinase Inhibitors therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Breast Neoplasms pathology, Estrogen Receptor alpha genetics, Cyclin-Dependent Kinase 4 antagonists & inhibitors, Cyclin-Dependent Kinase 4 genetics, Mutation, Cyclin-Dependent Kinase 6 antagonists & inhibitors, Cyclin-Dependent Kinase 6 genetics
- Abstract
Background: In estrogen receptor-positive metastatic breast cancer, ESR1 mutations (ESR1 m ) are a common mechanism of acquired resistance to aromatase inhibitors (ArIh). However, the impact ESR1 alterations have on CDK4/6 inhibitor (CDK4/6i) sensitivity has not been established. Analyses of CDK4/6i trials suggest that the endocrine therapy partner and specific ESR1 allele may affect susceptibility. We analyzed a real-world data set to investigate CDK4/6i efficacy in ESR1 m metastatic breast cancer and associated clinical factors., Methods: ESR1 m were identified by analysis of circulating-tumor deoxyribonucleic acid. The GuardantINFORM database contains genomic information from tumors linked with claims data. Patients who started a CDK4/6i within 30 days of sequencing were categorized as having ESR1 m or non- ESR1 -mutant (non-ESR1 m ) breast cancer. Data were analyzed to determine the real-world time-to-next-treatment, defined as the start of a breast cancer treatment to initiation of the subsequent treatment., Results: One hundred forty-five patients with ESR1 m and 612 with non-ESR1 m metastatic breast cancer were analyzed. ESR1 m and non-ESR1 m tumors had similar real-world time-to-next-treatment on CDK4/6i regimens (hazard ratio, 1.02; 95% confidence interval, 0.82 to 1.23). Duration on therapy in the first-line and second-line plus treatment settings were comparable regardless of ESR1 status. We stratified treatment duration by concurrent endocrine therapy, and patients with ESR1 m had worse outcomes on ArIh but comparable real-world time-to-next-treatment on fulvestrant., Conclusions: These data suggest ESR1 variants are not associated with pan-CDK4/6i resistance and are consistent with the hypothesis that CDK4/6 blockade combined with a selective estrogen receptor degrader is potentially an effective option for ESR1 m metastatic breast cancer.
- Published
- 2024
- Full Text
- View/download PDF