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Evaluation of alpelisib-induced hyperglycemia prophylaxis and associated risk factors in PIK3CA-mutated hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer

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Abstract

Purpose

SOLAR-1 investigated alpelisib-fulvestrant (ALP + FLV) in patients with HR + /HER2-, PIK3CA-mutated advanced breast cancer and demonstrated a clinically significant increase in all-grade and grade (G) 3-4 hyperglycemia (HG) compared to placebo-fulvestrant. Given high rates of HG, a preventative protocol and identification of associated risk factors was implemented.

Methods

This single-center, retrospective study included patients receiving ALP + FLV. One week before ALP initiation, patients started an insulin-sensitizer. Patients had fasting plasma glucose (FPG) levels drawn day 8, 15, 28, then monthly. Primary outcome was incidence of G2-4 HG by day 28. Risk factors assessed included age, BMI, FPG, and HbA1c. Number of risk factors were compared between patients with and without HG.

Results

Sixteen women were included with median age of 59 years. The cohort was 69% White, 25% Black, 75% with BMI ≥ 25 kg/m2, and 50% with history of diabetes. By day 28, 9 patients (56%) had G2-4 HG, with only 3 (19%) G3 and zero G4. Patients with G2-4 HG had a median of 2 risk factors compared to only 1 if no HG (p = 0.03). 5 patients (31%) required a temporary hold of ALP and 3 (19%) required dose reduction due to HG. 13 patients permanently discontinued ALP—9 due to disease progression and 4 from an adverse event (only 1 HG).

Conclusion

Implementation of a HG prophylaxis protocol with ALP in a single-center study demonstrated fewer G3-4 HG events compared to that seen in SOLAR-1 (19% vs 36.6%). An increase in HG-associated risk factors correlated with a higher incidence of G2-4 HG.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ADA:

American Diabetes Association

ALP:

Alpelisib

CTCAE:

Common Terminology Criteria for Adverse Events

DBOC:

Duke Breast Oncology Clinic

FLV:

Fulvestrant

FBG:

Fasting blood glucose

FPG:

Fasting plasma glucose

G:

Grade

HbA1c:

Hemoglobin A1c

HER2:

Human epidermal growth factor 2

HG:

Hyperglycemia

HR:

Hormone receptor

P:

Placebo

PI3K:

Phosphatidylinositol-3-kinase

REDCap:

Research electronic data capture

SGLT-2:

Sodium glucose cotransporter-2

T2DM:

Type 2 diabetes mellitus

XR:

Extended release

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Authors and Affiliations

  1. Department of Pharmacy, Atrium Health Wake Forest Baptist, 1 Medical Center Blvd, Winston Salem, NC, 27157, USA

    Sarah E. Burnette

  2. Department of Biostatistics and Bioinformatics, Duke University, 2424 Erwin Road, Hock Plaza Suite 1102, Durham, NC, 27710, USA

    Emily Poehlein & Hui-Jie Lee

  3. Department of Breast Oncology, Duke University Cancer Institute, Durham, NC, USA

    Jeremy Force & Kelly Westbrook

  4. Department of Pharmacy, Duke University Medical Center, 20 Duke Medicine Circle, Clinic 2-1, Durham, NC, 27710, USA

    Heather N. Moore

Authors
  1. Sarah E. Burnette
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  2. Emily Poehlein
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  3. Hui-Jie Lee
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  4. Jeremy Force
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  5. Kelly Westbrook
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Contributions

SB, HM, JF, and KW were responsible for concept and design of the study. SB contributed to collection of the data. EP and H-JL conducted statistical analysis of the data. All authors contributed to analysis and interpretation of the data. SB, with supervision from HM, drafted the manuscript. All authors critically reviewed the manuscript and approved the final version.

Corresponding author

Correspondence to Heather N. Moore.

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Conflict of interest

H Moore is an active consultant for Novartis Pharmaceuticals and serves on the EPIK-B4 steering committee and is active PI of EPIK-B4 at Duke University Hospital. S Burnette, HJ Lee, and E Poehlein, J Force, and K Westbrook have no conflicts of interest to report.

Ethical approval and consent to participate

All study protocols were reviewed and approved by Duke University Health System’s Institutional Review Board.

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Burnette, S.E., Poehlein, E., Lee, HJ. et al. Evaluation of alpelisib-induced hyperglycemia prophylaxis and associated risk factors in PIK3CA-mutated hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer. Breast Cancer Res Treat 197, 369–376 (2023). https://doi.org/10.1007/s10549-022-06798-8

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  • DOI: https://doi.org/10.1007/s10549-022-06798-8

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