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Everolimus in Advanced Breast Cancer: A Systematic Review and Meta-analysis

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Abstract

Background

Everolimus plus exemestane is approved for the treatment of hormone receptor-positive metastatic breast cancer (MBC) after progression on nonsteroidal aromatase inhibitors. The role of everolimus is less well defined in other breast cancer phenotypes and in combination with other drugs.

Objectives

We conducted a systematic review and meta-analysis to assess the efficacy and safety of adding everolimus to standard of care (SoC) in MBC regardless of tumor phenotype and treatment type.

Methods

The electronic databases PubMed and EMBASE were searched for eligible randomized trials. Pooled hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) and pooled risk ratios (RR) and odds ratios for objective response rates, disease control rate (DCR), and grade 3 or higher toxicity were meta-analyzed. Subgroup analyses compared survival outcomes by tumor phenotype.

Results

Data from 2826 patients from eight trials were analyzed. The addition of everolimus to SoC reduced the risk of disease progression by 29% (HR 0.71; 95% confidence interval [CI] 0.56–0.90). This did not translate into an OS benefit (HR 0.95; 95% CI 0.80–1.13). In addition, everolimus improved the DCR (RR 0.82; 95% CI 0.68–0.98), whereas it increased the risk of developing grade 3 or higher toxicity. The PFS benefit was more prominent for patients with hormone receptor-positive (+)/human epidermal growth factor receptor 2 (HER2)-negative (−) disease. For the HER2 (+) subgroup, the PFS benefit was restricted to patients with hormone receptor (−) disease.

Conclusions

Everolimus reduces the risk of disease progression in hormone receptor (+) MBC. In patients with HER2 (+) disease, the benefit is limited for those with hormone receptor (−) disease. Given the approval and use of newer drugs in MBC, clinical trials and real-world data are needed to confirm the benefit of everolimus and define the best treatment sequence strategy to adopt in that setting.

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Authors and Affiliations

  1. Division of Medical Oncology, Department of Oncology, Western University, London Regional Cancer Program, 800 Commissioners road east, London, ON, N6A 5W9, Canada

    Jacques Raphael, Gabriel Boldt, Theodore Vandenberg & Phillip S Blanchette

  2. Department of Anatomy and Cell Biology, Western University, London, ON, Canada

    Cory Lefebvre & Alison Allan

  3. Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada

    Joelle Helou

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  1. Jacques Raphael
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Correspondence to Jacques Raphael.

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No external funding was used in the preparation of this manuscript.

Conflict of interest

Jacques Raphael has received honorarium (Hoffmann-La Roche) and participated on an advisory board for Lilly Oncology. Cory Lefebvre, Alison Allan, Joelle Helou, Gabriel Boldt, Theodore Vandenberg, and Phillip S. Blanchette have no conflicts of interest that might be relevant to the contents of this manuscript.

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Author contributions

JR had the idea for the systemic review; JR, C.L, GB performed the literature search and data analysis, JR, CL, GB, JH, A.A, PB, and TV drafted and critically revised the work.

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Raphael, J., Lefebvre, C., Allan, A. et al. Everolimus in Advanced Breast Cancer: A Systematic Review and Meta-analysis. Targ Oncol 15, 723–732 (2020). https://doi.org/10.1007/s11523-020-00770-6

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