Jacques Raphael1, Cory Lefebvre2, Alison Allan2, Joelle Helou3, Gabriel Boldt4, Theodore Vandenberg4, Phillip S Blanchette4. 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@lhsc.on.ca. 2. Department of Anatomy and Cell Biology, Western University, London, ON, Canada. 3. Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada. 4. Division of Medical Oncology, Department of Oncology, Western University, London Regional Cancer Program, 800 Commissioners road east, London, ON, N6A 5W9, Canada.
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.
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.
Authors: Abeer Alqaisi; Li Chen; Edward Romond; Mara Chambers; Mark Stevens; Grace Pasley; Mukta Awasthi; Suleiman Massarweh Journal: Breast Cancer Res Treat Date: 2014-09-26 Impact factor: 4.872
Authors: Alessandro Liberati; Douglas G Altman; Jennifer Tetzlaff; Cynthia Mulrow; Peter C Gøtzsche; John P A Ioannidis; Mike Clarke; P J Devereaux; Jos Kleijnen; David Moher Journal: PLoS Med Date: 2009-07-21 Impact factor: 11.069
Authors: Denise A Yardley; Shinzaburo Noguchi; Kathleen I Pritchard; Howard A Burris; José Baselga; Michael Gnant; Gabriel N Hortobagyi; Mario Campone; Barbara Pistilli; Martine Piccart; Bohuslav Melichar; Katarina Petrakova; Francis P Arena; Frans Erdkamp; Wael A Harb; Wentao Feng; Ayelet Cahana; Tetiana Taran; David Lebwohl; Hope S Rugo Journal: Adv Ther Date: 2013-10-25 Impact factor: 3.845
Authors: Qing-Bai She; Sofia K Gruvberger-Saal; Matthew Maurer; Yilun Chen; Mervi Jumppanen; Tao Su; Meaghan Dendy; Ying-Ka Ingar Lau; Lorenzo Memeo; Hugo M Horlings; Marc J van de Vijver; Jorma Isola; Hanina Hibshoosh; Neal Rosen; Ramon Parsons; Lao H Saal Journal: BMC Cancer Date: 2016-08-02 Impact factor: 4.430