Clinical management of common toxicities with inhibitors targeting the PI3K/AKT/mTOR pathway in breast cancer

Jhaveri KL, Iyengar NM, Turner NC, Rugo HS, O'Shaughnessy J, Barrios CH, Curigliano G, André F, Im SA, Goncalves MD, Lacouture ME, Fasching P, Leung R (2026)

Publication Type: Journal article, Review article

Publication year: 2026

Journal

ESMO Open BMJ Publishing Group

Book Volume: 11

Article Number: 105936

Journal Issue: 2

DOI: 10.1016/j.esmoop.2025.105936

Abstract

Dysregulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway has been implicated in oncogenesis, treatment resistance, and disease progression, making it an attractive target for anticancer drug development. Early experiences with PI3K/AKT/mTOR inhibitors have highlighted challenges associated with their modest efficacy, as well as safety and tolerability issues; however, several effective next-generation PI3K/AKT/mTOR inhibitors have now been approved for patients with breast cancer. As a result, there is a growing need to understand the presentation, characteristics, and management of common toxicities (hyperglycemia, rash, stomatitis, and diarrhea). This review summarizes available safety data from phase III randomized clinical trials for approved PI3K/AKT/mTOR pathway-targeted therapies (everolimus, alpelisib, capivasertib, and inavolisib), including incidence, severity, adverse event-related dose modifications, and time to onset. We also provide guidance for preparation, monitoring, and management strategies for integrating these therapies into clinical practice, with the hope that appropriate support will allow patients to tolerate higher PI3K/AKT/mTOR inhibitor dose intensities, which has the potential to translate to improved patient outcomes.

Authors with CRIS profile

Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe

Involved external institutions

Weill Cornell Medicine US United States (USA) (US) Royal Marsden Hospital / The Royal Marsden NHS Foundation Trust GB United Kingdom (GB) City of Hope Medical Center US United States (USA) (US) Baylor University Medical Center US United States (USA) (US) LACOG - Latin American Cooperative Oncology Group BR Brazil (BR) Università degli studi di Milano IT Italy (IT) Institut Gustave-Roussy FR France (FR) Seoul National University (SNU) / 서울대학교 KR Korea, Republic of (KR) New York University (NYU) US United States (USA) (US) The University of Hong Kong (HKU) / 香港大學 HK Hong Kong (HK) Memorial Sloan Kettering Cancer Center US United States (USA) (US)

How to cite

APA:

Jhaveri, K.L., Iyengar, N.M., Turner, N.C., Rugo, H.S., O'Shaughnessy, J., Barrios, C.H.,... Leung, R. (2026). Clinical management of common toxicities with inhibitors targeting the PI3K/AKT/mTOR pathway in breast cancer. ESMO Open, 11(2). https://doi.org/10.1016/j.esmoop.2025.105936

MLA:

Jhaveri, K. L., et al. "Clinical management of common toxicities with inhibitors targeting the PI3K/AKT/mTOR pathway in breast cancer." ESMO Open 11.2 (2026).

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