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Factors leading to alpelisib discontinuation in patients with hormone receptor positive, human epidermal growth factor receptor-2 negative breast cancer

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Abstract

Purpose

Alpelisib is a phosphoinositide-3-kinase inhibitor approved for hormone-receptor-positive, PIK3CA-mutated metastatic breast cancer. However, length of drug exposure, maximum-tolerated dose, and therefore clinical response can vary significantly outside of the trial setting. This study evaluates our center’s “real world” experience with alpelisib and focuses on duration of therapy and factors associated with cancer progression.

Methods

Patients receiving alpelisib at our center between 2019 and 2021 were identified. We evaluated duration of alpelisib therapy and the causative reasons for drug discontinuation. The association of drug duration and dose with subsequent cancer progression were assessed, along with the association between hyperglycemia during alpelisib therapy and cancer progression.

Results

Sixty-two women prescribed alpelisib were included (mean age 61 years). Disease progression was the most common reason for drug discontinuation, while discontinuation within 30 days was primarily attributed to adverse events (AEs). Among those who progressed, median time to progression was longer in those on alpelisib for > 90 days compared with those on alpelisib for ≤ 90 days (187 vs. 77 days, p < 0.001). At 200 days, freedom from progression was greater for those on alpelisib for > 90 days compared to those receiving therapy for ≤ 90 days (59% vs. 19%, p = 0.001). Median blood glucose as a continuous variable was associated with disease progression (HR 1.01, 95% CI 1.00–1.02, p = 0.02).

Conclusion

While progression of disease is the largest contributor to alpelisib discontinuation, AEs are the leading cause for early drug cessation. Shorter alpelisib exposure is associated with greater cancer progression. Further studies are needed to determine the impact of sustained hyperglycemia on cancer progression.

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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.

Code availability

All statistical methods and codes are available for review upon request.

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Acknowledgements

There are no additional acknowledgements to disclose.

Funding

No funding was received for the conduction of this study.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, 221 Longwood Ave, Boston, MA, 02115, USA

    Yee-Ming M. Cheung, Grace E. Cromwell, Le Min & Marie E. McDonnell

  2. Department of Medicine, Endocrine Unit, Austin Hospital, The University of Melbourne, Victoria, Australia

    Yee-Ming M. Cheung

  3. Department of Medical Oncology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA, 02215, USA

    Sara M. Tolaney

Authors
  1. Yee-Ming M. Cheung
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  2. Grace E. Cromwell
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  3. Sara M. Tolaney
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  4. Le Min
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  5. Marie E. McDonnell
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Y-MC and GC. The first draft of the manuscript was written by Y-MC and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Marie E. McDonnell.

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Conflict of interest

SMT receives institutional research funding from AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, Exelixis, Bristol-Myers Squibb, Eisai, Nanostring, Cyclacel, Odonate, and Seattle Genetics; has served as an advisor/consultant to AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, Bristol-Myers Squibb, Eisai, Nanostring, Puma, Sanofi, Celldex, Paxman, Puma, Silverback Therapeutics, G1 Therapeutics, Gilead, AbbVie, Athenex, OncoPep, Outcomes4Me, Kyowa Kirin Pharmaceuticals, Daiichi-Sankyo, and Samsung Bioepsis Inc. All other authors have no funding or conflicts of interest to disclose.

Ethical approval

This study has been approved by the MassGeneralBrigham Institutional Review Board (IRB).

Informed consent

Given the retrospective and low risk nature of this study, formal participant consent and consent to publish was not required.

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Cheung, YM.M., Cromwell, G.E., Tolaney, S.M. et al. Factors leading to alpelisib discontinuation in patients with hormone receptor positive, human epidermal growth factor receptor-2 negative breast cancer. Breast Cancer Res Treat 192, 303–311 (2022). https://doi.org/10.1007/s10549-021-06476-1

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  • DOI: https://doi.org/10.1007/s10549-021-06476-1

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