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Current Oncology is published by MDPI from Volume 28 Issue 1 (2021). Previous articles were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence, and they are hosted by MDPI on mdpi.com as a courtesy and upon agreement with Multimed Inc..
Article

Novel Agents and Associated Toxicities of Inhibitors of the PI3K/Akt/mTOR Pathway for the Treatment of Breast Cancer

1
Department of Medical Oncology, BC Cancer Agency, Vancouver, BC, Canada
2
Sunnybrook Health Sciences Centre and University of Toronto, Toronto, ON, Canada
3
Department of Oncology, Division of Medical Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB, Canada
4
Eastern Health, St. John’s, NL, Canada
5
Royal Victoria Regional Health Centre, Barrie, ON, Canada
6
SNELL Medical Communication, Montreal, QC, Canada
7
Centre hospitalier de l’Université de Montréal–Hôpital Notre-Dame, Montreal, QC, Canada
8
Grand River Regional Cancer Centre, Kitchener, ON, Canada
9
Division of Medical Oncology, Dalhousie University, and Atlantic Clinical Cancer Research Unit, Halifax, NS, Canada
10
The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada
*
Author to whom correspondence should be addressed.
Curr. Oncol. 2015, 22(1), 33-48; https://doi.org/10.3747/co.22.2393
Received: 5 November 2014 / Revised: 10 December 2014 / Accepted: 3 January 2015 / Published: 1 February 2015
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.
Keywords: breast cancer; pi3k/Akt/mtor; everolimus; adverse events breast cancer; pi3k/Akt/mtor; everolimus; adverse events
MDPI and ACS Style

Chia, S.; Gandhi, S.; Joy, A.A.; Edwards, S.; Gorr, M.; Hopkins, S.; Kondejewski, J.; Ayoub, J.P.; Califaretti, N.; Rayson, D.; Dent, S.F. Novel Agents and Associated Toxicities of Inhibitors of the PI3K/Akt/mTOR Pathway for the Treatment of Breast Cancer. Curr. Oncol. 2015, 22, 33-48. https://doi.org/10.3747/co.22.2393

AMA Style

Chia S, Gandhi S, Joy AA, Edwards S, Gorr M, Hopkins S, Kondejewski J, Ayoub JP, Califaretti N, Rayson D, Dent SF. Novel Agents and Associated Toxicities of Inhibitors of the PI3K/Akt/mTOR Pathway for the Treatment of Breast Cancer. Current Oncology. 2015; 22(1):33-48. https://doi.org/10.3747/co.22.2393

Chicago/Turabian Style

Chia, S., S. Gandhi, A.A. Joy, S. Edwards, M. Gorr, S. Hopkins, J. Kondejewski, J.P. Ayoub, N. Califaretti, D. Rayson, and S.F. Dent 2015. "Novel Agents and Associated Toxicities of Inhibitors of the PI3K/Akt/mTOR Pathway for the Treatment of Breast Cancer" Current Oncology 22, no. 1: 33-48. https://doi.org/10.3747/co.22.2393

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