CDK4/6 Inhibitor Efficacy in ESR1 -Mutant Metastatic Breast Cancer.

Autor:	Lloyd MR; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston., Brett JO; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston.; Dana-Farber Cancer Institute, Harvard Medical School, Boston., Carmeli A; The Broad Institute of MIT and Harvard, Cambridge, MA.; Count Me In: Patient-Partnered Research, Cambridge, MA., Weipert CM; Guardant Health, Palo Alto, CA., Zhang N; Guardant Health, Palo Alto, CA., Yu J; Guardant Health, Palo Alto, CA., Bucheit L; Guardant Health, Palo Alto, CA., Medford AJ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston., Wagle N; Dana-Farber Cancer Institute, Harvard Medical School, Boston.; Genentech, South San Francisco, CA., Bardia A; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston., Wander SA; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston.
Jazyk:	angličtina
Zdroj:	NEJM evidence [NEJM Evid] 2024 May; Vol. 3 (5), pp. EVIDoa2300231. Date of Electronic Publication: 2024 Apr 23.
DOI:	10.1056/EVIDoa2300231
Abstrakt:	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.
Databáze:	MEDLINE
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