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Cited by 36Advanced Breast Cancer TherapiesPI3K/AKT/mTOR signaling in cancerChemotherapy-related skin toxicity

Managing hyperglycemia and rash associated with alpelisib: expert consensus recommendations using the Delphi technique

Open access
Gallagher, Emily J., Moore, Heather, Lacouture, Mario E., Dent, Susan F., Farooki, Azeez, Goncalves, Marcus D., Isaacs, Claudine, Johnston, Abigail +12 more·2024·npj Breast Cancer
DOI 10.1038/s41523-024-00613-xPMC PMC10831089
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Abstract

Hyperglycemia and rash are expected but challenging adverse events of phosphatidylinositol-3-kinase inhibition (such as with alpelisib). Two modified Delphi panels were conducted to provide consensus recommendations for managing hyperglycemia and rash in patients taking alpelisib. Experts rated the appropriateness of interventions on a 1-to-9 scale; median scores and dispersion were used to classify the levels of agreement. Per the hyperglycemia panel, it is appropriate to start alpelisib in patients with HbA1c 6.5% (diabetes) to <8%, or at highest risk for developing hyperglycemia, if they have a pre-treatment endocrinology consult. Recommend prophylactic metformin in patients with baseline HbA1c 5.7% to 6.4%. Metformin is the preferred first-line anti-hyperglycemic agent. Per the rash panel, initiate prophylactic nonsedating H1 antihistamines in patients starting alpelisib. Nonsedating H1 antihistamines and topical steroids are the preferred initial management for rash. In addition to clinical trial evidence, these recommendations will help address gaps encountered in clinical practice.

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  • Insulin can reactivate the PI3K pathway, negating the effects of alpelisib.

    “Insulin and sulfonylureas should be considered last-line agents, as insulin can reactivate the PI3K pathway, negating the effects of alpelisib (223,224).”

    From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [223]

    The Introduction says preclinical data suggest that compensatory hyperinsulinemia can partially reactivate the PI3K pathway; the Results also warn that insulin carries a potential risk of pathway stimulation. The paper does not say insulin negates alpelisib’s effects. Its Results generally advise against insulin and sulfonylureas as first- or second-line agents, but allow insulin in some circumstances. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Metformin is the first-line oral agent to treat alpelisib-induced hyperglycemia.

    “Metformin is the first-line oral agent to treat alpelsib-induced hyperglycemia, and prophylactic initiation of metformin has been recommended for people with prediabetes receiving alpelsib (223).”

    From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [223]

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Cited by

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Authors
Gallagher, E. J., Moore, H., Lacouture, M. E., Dent, S. F., Farooki, A., Goncalves, M. D., Isaacs, C., Johnston, A., Juric, D., Quandt, Z., Spring, L., Berman, B., Decker, M., Hortobagyi, G. N., Kaffenberger, B. H., Kwong, B. Y., Pluard, T., Rao, R., Schwartzberg, L., & Broder, M. S.
Affiliations
  • Tisch Cancer Institute (US)
  • Duke University (US)
  • Memorial Sloan Kettering Cancer Center (US)
  • Weill Cornell Medicine (US)
  • Georgetown University (US)
  • Harvard University (US)
  • University of California, San Francisco (US)
  • University of Miami (US)
  • Kaiser Permanente (US)
  • The Ohio State University Wexner Medical Center (US)
  • Stanford Medicine (US)
  • Saint Luke's Hospital (US)
  • Rush University Medical Center (US)
  • West Cancer Center (US)
  • Partnership for Health Analytic Research (US)
Corresponding author
Gallagher, Emily J.
ORCID
Venue
npj Breast Cancer
Publisher
Springer Science and Business Media LLC
Published
2024-01-31
Volume
10
Issue
1
Pages
12-12
ISSN
2374-4677 (ISSN-L)
DOI
10.1038/s41523-024-00613-x
PMC
PMC10831089
OpenAlex
W4391383971
Cited by
36
References
3
Citations by year
2026: 17 · 2025: 14 · 2024: 5
FWCI
10.46
Type
journal article
Language
en
Open access
Licence
Locations
  • npj Breast Cancer (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Novartis Pharmaceuticals Corporation
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Health Sciences › Medicine › Dermatology › Chemotherapy-related skin toxicity
Keywords
alpelisib, hyperglycemia, cutaneous adverse events, rash, PI3K inhibitors, histamine H1 receptor antagonists, topical corticosteroids, endocrinology consultation, HbA1c, breast cancer, expert consensus recommendations

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