LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases.

Autor: Van Swearingen AED; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Siegel MB; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Deal AM; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Sambade MJ; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Hoyle A; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Hayes DN; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA.; West Cancer Center, University of Tennessee, Knoxville, USA., Jo H; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Little P; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Dees EC; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Muss H; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Jolly T; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Zagar TM; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Patel N; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Miller CR; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Parker JS; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Smith JK; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Fisher J; Carolinas Medical Center, Charlotte, NC, USA., Shah N; MD Anderson Orlando, Orlando, FL, USA., Nabell L; University of Alabama, Birmingham, AL, USA., Nanda R; University of Chicago, Chicago, IL, USA., Dillon P; University of Virginia, Charlottesville, VA, USA., Abramson V; Vanderbilt University, Nashville, TN, USA., Carey LA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA., Anders CK; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 170 Manning Drive, CB #7305, Chapel Hill, NC, 27599-7305, USA. carey_anders@med.unc.edu.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2018 Oct; Vol. 171 (3), pp. 637-648. Date of Electronic Publication: 2018 Jun 25.
DOI: 10.1007/s10549-018-4852-5
Abstrakt: Purpose: HER2 + breast cancer (BC) is an aggressive subtype with high rates of brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study evaluated everolimus (E), a brain-permeable mTOR inhibitor, trastuzumab (T), and vinorelbine (V) in patients with HER2 + BCBM.
Patients and Methods: Eligible patients had progressive HER2 + BCBM. The primary endpoint was intracranial response rate (RR); secondary objectives were CNS clinical benefit rate (CBR), extracranial RR, time to progression (TTP), overall survival (OS), and targeted sequencing of tumors from enrolled patients. A two-stage design distinguished intracranial RR of 5% versus 20%.
Results: 32 patients were evaluable for toxicity, 26 for efficacy. Intracranial RR was 4% (1 PR). CNS CBR at 6 mos was 27%; at 3 mos 65%. Median intracranial TTP was 3.9 mos (95% CI 2.2-5). OS was 12.2 mos (95% CI 0.6-20.2). Grade 3-4 toxicities included neutropenia (41%), anemia (16%), and stomatitis (16%). Mutations in TP53 and PIK3CA were common in BCBM. Mutations in the PI3K/mTOR pathway were not associated with response. ERBB2 amplification was higher in BCBM compared to primary BC; ERBB2 amplification in the primary BC trended toward worse OS.
Conclusion: While intracranial RR to ETV was low in HER2 + BCBM patients, one-third achieved CNS CBR; TTP/OS was similar to historical control. No new toxicity signals were observed. Further analysis of the genomic underpinnings of BCBM to identify tractable prognostic and/or predictive biomarkers is warranted.
Clinical Trial: (NCT01305941).
Databáze: MEDLINE
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