Novel agents and associated toxicities of inhibitors of the pi3k/Akt/mtor pathway for the treatment of breast cancer

  • S. Chia Department of Medical Oncology, BC Cancer Agency, Vancouver
  • S. Gandhi Sunnybrook Health Sciences Centre and the University of Toronto
  • A.A. Joy Department of Oncology, Division of Medical Oncology, University of Alberta, Cross Cancer Institute
  • S. Edwards Eastern Health
  • M. Gorr Royal Victoria Regional Health Centre
  • S. Hopkins Royal Victoria Regional Health Centre
  • J. Kondejewski Snell Medical Communication Inc, Montreal
  • J.P. Ayoub Centre hospitalier de l'Université de Montréal - Hôpital Notre-Dame
  • N. Califaretti Grand River Regional Cancer Centre
  • D. Rayson Division of Medical Oncology, Dalhousie University and Atlantic Clinical Cancer Research Unit
  • S. Dent The Ottawa Hospital Cancer Centre
Keywords: breast cancer, pi3k/Akt/mtor, everolimus, adverse events

Abstract

The pi3k/Akt/mtor (phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin) signalling pathway is an established driver of oncogenic activity in human malignancies. Therapeutic targeting of this pathway holds significant promise as a treatment strategy. Everolimus, an mtor inhibitor, is the first of this class of agents approved for the treatment of hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer. Everolimus has been associated with significant improvements in progression-free survival; however, it is also associated with increased toxicity related to its specific mechanism of action.

Methods

A comprehensive review of the literature conducted using a focused medline search was combined with a search of current trials at http://ClinicalTrials. gov/. Summary tables of the toxicities of the various classes of pi3k/Akt/mtor inhibitors were created. A broad group of Canadian health care professionals was assembled to review the data and to produce expert opinion and summary recommendations for possible best practices in managing the adverse events associated with these pathway inhibitors.

Results

Differing toxicities are associated with the various classes of pi3k/Akt/mtor pathway inhibitors. The most common unique adverse events observed in everolimus clinical trials in breast cancer include stomatitis (all grades: approximately 60%), noninfectious pneumonitis (15%), rash (40%), hyperglycemia (15%), and immunosuppression (40%). To minimize grades 3 and 4 toxicities and to attempt to attain optimal outcomes, effective management of those adverse events is critical. Management should be interdisciplinary and should use approaches that include education, early recognition, active intervention, and potentially prophylactic strategies.

Discussion

Everolimus likely represents the first of many complex oral targeted therapies for the treatment of breast cancer. Using this agent as a template, it is essential to establish best practices involving and integrating multiple disciplines for the management of future pi3k/Akt/mtor signalling pathway inhibitors.

Author Biographies

S. Chia, Department of Medical Oncology, BC Cancer Agency, Vancouver
Associate Professor of Medicine, BC Cancer Agency, University of British Columbia
S. Gandhi, Sunnybrook Health Sciences Centre and the University of Toronto

Medical Oncologist, Sunnybrook Odette Cancer Centre

Assistant Professor, Department of Medicine

M. Gorr, Royal Victoria Regional Health Centre

Oral Therapy Nurse Navigator

Royal Victoria Regional Health Centre

J.P. Ayoub, Centre hospitalier de l'Université de Montréal - Hôpital Notre-Dame
Oncologue médical, Service d'Hémato-oncologie
S. Dent, The Ottawa Hospital Cancer Centre

Medical Oncologist

The Ottawa Hospital Cancer Centre

Associate Professor of Medicine, University of Ottawa

Vice-Chair Patient Quality and Safety, Department of Medicine

Founder, Canadian Cardiac Oncology Network

Published
2015-01-13
How to Cite
Chia, S., Gandhi, S., Joy, A., Edwards, S., Gorr, M., Hopkins, S., Kondejewski, J., Ayoub, J., Califaretti, N., Rayson, D., & Dent, S. (2015). Novel agents and associated toxicities of inhibitors of the pi3k/Akt/mtor pathway for the treatment of breast cancer. Current Oncology, 22(1), 33-48. https://doi.org/10.3747/co.22.2393
Section
Review Article