Phase II trial of fulvestrant plus enzalutamide in ER+/HER2- advanced breast cancer.

Autor: Elias AD; Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. anthony.elias@cuanschutz.edu., Spoelstra NS; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Staley AW; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Sams S; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Crump LS; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Vidal GA; West Cancer Center and Research Institute and Dept of Medicine, University of Tennessee Health Sciences Center, Germantown, TN, USA., Borges VF; Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Kabos P; Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Diamond JR; Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Shagisultanova E; Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Afghahi A; Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Mayordomo J; Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., McSpadden T; University of Colorado Cancer Center, Oncology Clinical Research Support Team, Anschutz Medical Campus, Aurora, CO, USA., Crawford G; University of Colorado Cancer Center, Cancer Clinical Trials Office, Anschutz Medical Campus, Aurora, CO, USA., D'Alessandro A; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Zolman KL; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., van Bokhoven A; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Zhuang Y; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Gallagher RI; Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA., Wulfkuhle JD; Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA., Petricoin Iii EF; Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA., Gao D; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Richer JK; Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Jazyk: angličtina
Zdroj: NPJ breast cancer [NPJ Breast Cancer] 2023 May 20; Vol. 9 (1), pp. 41. Date of Electronic Publication: 2023 May 20.
DOI: 10.1038/s41523-023-00544-z
Abstrakt: This clinical trial combined fulvestrant with the anti-androgen enzalutamide in women with metastatic ER+/HER2- breast cancer (BC). Eligible patients were women with ECOG 0-2, ER+/HER2- measurable or evaluable metastatic BC. Prior fulvestrant was allowed. Fulvestrant was administered at 500 mg IM on days 1, 15, 29, and every 4 weeks thereafter. Enzalutamide was given at 160 mg po daily. Fresh tumor biopsies were required at study entry and after 4 weeks of treatment. The primary efficacy endpoint of the trial was the clinical benefit rate at 24 weeks (CBR24). The median age was 61 years (46-87); PS 1 (0-1); median of 4 prior non-hormonal and 3 prior hormonal therapies for metastatic disease. Twelve had prior fulvestrant, and 91% had visceral disease. CBR24 was 25% (7/28 evaluable). Median progression-free survival (PFS) was 8 weeks (95% CI: 2-52). Adverse events were as expected for hormonal therapy. Significant (p < 0.1) univariate relationships existed between PFS and ER%, AR%, and PIK3CA and/or PTEN mutations. Baseline levels of phospho-proteins in the mTOR pathway were more highly expressed in biopsies of patients with shorter PFS. Fulvestrant plus enzalutamide had manageable side effects. The primary endpoint of CBR24 was 25% in heavily pretreated metastatic ER+/HER2- BC. Short PFS was associated with activation of the mTOR pathway, and PIK3CA and/or PTEN mutations were associated with an increased hazard of progression. Thus, a combination of fulvestrant or other SERD plus AKT/PI3K/mTOR inhibitor with or without AR inhibition warrants investigation in second-line endocrine therapy of metastatic ER+ BC.
(© 2023. The Author(s).)
Databáze: MEDLINE
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