NE Oncology Issue – February 2014

Safra T, et al. ECC 2013:1895


Approximately 75% of advanced breast cancers (ABC) in post-menopausal women are estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2–). Currently, there is an unmet medical need for new treatment modalities after failure of endocrine therapy. Activation of the mTOR pathway is a key adaptive change driving endocrine resistance. Preclinical and early clinical data suggest a synergism between RAD001 (everolimus) and letrozole resulting in restoration of sensitivity to endocrine therapy.1

Study design

  • This was a multicentre, Israeli, open-label, phase II study evaluating treatment with everolimus (oral 10 mg/day) combined with letrozole (oral 2.5 mg/day) in post-menopausal women with ABC after progression on tamoxifen and/or anastrozole and/or letrozole and/or fulvestrant and/or exemestane.
  • The objectives were to assess overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the safety profile of the combination after failure of one or more endocrine therapies. Analysis was performed on the intent-to-treat population.

Key findings

  • A total of 73 patients were enrolled.
  • The patients’ baseline characteristics included:
    • Median age: 55 (28–80) years;
    • All had ABC with one to three metastatic sites;
    • Patients were previously exposed to a median of 2 (1–5) lines of hormonal therapy; 54% to letrozole.
  • At the time of analysis, the median follow-up was 12.23 (2–22) months.
  • Responses to treatment were:
    • ORR: 19% (15/73);
    • DCR: 58% (43/73); and
    • Progressive disease: 25% (18/73).
  • PFS was 7.9 (1–22) months, while 25% (18/73) of patients are still on treatment.
  • OS is too early to evaluate, with 78% of patients still alive.
  • Commonly observed all-grade toxicities included: stomatitis (50%), weakness (50%), weight loss (30%), anorexia (27%), anemia (28%), hyperlipidemia (23%), diarrhea (19%), myalgia/arthralgia (16%), and pneumonitis (10%).

Key conclusions

  • These preliminary results are consistent with BOLERO-2 findings,2 showing significant prolongation of PFS and an acceptable toxicity profile with the addition of everolimus to an aromatase inhibitor in post-menopausal women with ER+/HER2– ABC who have progressed following previous endocrine therapy.
  • Longer follow-up and further evaluation is warranted.

References: 1. Safra T, Kadouri-Sonenfeld L, Ben Baruch N, et al. RAD001 (everolimus) in combination with letrozole in the treatment of hormone receptor positive HER2-negative postmenopausal women (PMW) with advanced breast cancer (ABC) after failure of endocrine therapy — a phase I study. ECC 2013:1895. 2. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor–positive advanced breast cancer. N Engl J Med 2012;366:520–9.

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Spotlight Article


Carolyn Owen, MD

Dr. Carolyn Owen completed postgraduate training in internal medicine and hematology at the University of Ottawa and the University of British Columbia, respectively, followed by a research fellowship in molecular genetics at Barts and the London School of Medicine and Dentistry in London, UK. Her research focused on familial myelodysplasia and acute myeloid leukemia. She is currently an Assistant Professor at the Foothills Medical Centre & Tom Baker Cancer Centre, and her clinical interests are low-grade lymphoma and chronic lymphocytic leukemia. She is also the local principal investigator in Calgary for several clinical trials in these areas.



Laurie H. Sehn, MD, MPH
Dr. Laurie H. Sehn is a Clinical Assistant Professor at the BC Cancer Agency and the University of British Columbia in Vancouver. She has been a medical oncologist and clinical investigator with the Lymphoma Tumour Group since 1998. Dr. Sehn has served on the Board of Directors of Lymphoma Foundation Canada (LFC) since 2002 and is currently Director of Research Fellowships for the LFC. Dr. Sehn’s research interests include all of the lymphoid cancers, with particular interest in the biology and treatment of large-cell lymphoma, the application of new imaging techniques such as PET scanning to lymphoma management, and innovative new approaches to treatment.

Canadian Perspective


Matthew Seftel, MBChB, MPH, MRCP(U.K.), FRCPC

Dr. Seftel is a hematologist/oncologist based at Princess Margaret Hospital in Toronto. He is a member of the Leukemia Group and leads the Allogeneic Blood and Marrow Transplantation Program. He is an Associate Professor at the University of Toronto in the Division of Internal Medicine. He is actively involved in clinical trials and outcomes-based research related to hematological malignancies and blood and marrow transplantation.

Investigator Commentary


Sunil Verma, MD, MSEd, FRCPC

Dr. Sunil Verma is a medical oncologist and the Chair of Breast Medical Oncology at the Sunnybrook Odette Cancer Centre in Toronto, Ontario. He is also an Associate Professor at the University of Toronto. Dr. Verma completed his medical degree and postgraduate training in internal medicine and medical oncology at the University of Alberta. He completed a fellowship in breast cancer at the University of Toronto and a master’s degree in medical education at the University of Southern California. Dr. Verma is internationally recognized for his educational leadership and research in breast and lung cancers. He has led and created numerous innovative educational projects in oncology and won several teaching and mentoring awards. Dr. Verma’s research interests include reducing the toxicity of systemic treatment, developing novel therapies for breast and lung cancers, and medical education. He is the principal investigator for many clinical trials in breast and lung cancers, including an international phase III trial in breast cancer, and has authored or co-authored articles appearing in publications such as the Journal of Clinical Oncology, Cancer, The Oncologist, Lancet Oncology, Lancet, and The New England Journal of Medicine.