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

Publication ,  Journal Article
Van Swearingen, AED; Siegel, MB; Deal, AM; Sambade, MJ; Hoyle, A; Hayes, DN; Jo, H; Little, P; Dees, EC; Muss, H; Jolly, T; Zagar, TM ...
Published in: Breast cancer research and treatment
October 2018

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.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%.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.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.(NCT01305941).

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Published In

Breast cancer research and treatment

DOI

EISSN

1573-7217

ISSN

0167-6806

Publication Date

October 2018

Volume

171

Issue

3

Start / End Page

637 / 648

Related Subject Headings

  • Vinorelbine
  • Treatment Outcome
  • Trastuzumab
  • Survival Analysis
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Mutation
  • Molecular Targeted Therapy
 

Citation

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Van Swearingen, A. E. D., Siegel, M. B., Deal, A. M., Sambade, M. J., Hoyle, A., Hayes, D. N., … Anders, C. K. (2018). LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases. Breast Cancer Research and Treatment, 171(3), 637–648. https://doi.org/10.1007/s10549-018-4852-5
Van Swearingen, Amanda E. D., Marni B. Siegel, Allison M. Deal, Maria J. Sambade, Alan Hoyle, D Neil Hayes, Heejoon Jo, et al. “LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases.Breast Cancer Research and Treatment 171, no. 3 (October 2018): 637–48. https://doi.org/10.1007/s10549-018-4852-5.
Van Swearingen AED, Siegel MB, Deal AM, Sambade MJ, Hoyle A, Hayes DN, et al. LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases. Breast cancer research and treatment. 2018 Oct;171(3):637–48.
Van Swearingen, Amanda E. D., et al. “LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases.Breast Cancer Research and Treatment, vol. 171, no. 3, Oct. 2018, pp. 637–48. Epmc, doi:10.1007/s10549-018-4852-5.
Van Swearingen AED, Siegel MB, Deal AM, Sambade MJ, Hoyle A, Hayes DN, Jo H, Little P, Dees EC, Muss H, Jolly T, Zagar TM, Patel N, Miller CR, Parker JS, Smith JK, Fisher J, Shah N, Nabell L, Nanda R, Dillon P, Abramson V, Carey LA, Anders CK. LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases. Breast cancer research and treatment. 2018 Oct;171(3):637–648.
Journal cover image

Published In

Breast cancer research and treatment

DOI

EISSN

1573-7217

ISSN

0167-6806

Publication Date

October 2018

Volume

171

Issue

3

Start / End Page

637 / 648

Related Subject Headings

  • Vinorelbine
  • Treatment Outcome
  • Trastuzumab
  • Survival Analysis
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Mutation
  • Molecular Targeted Therapy