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

Breast Cancer Res Treat. 2022 Apr;192(2):303-311. doi: 10.1007/s10549-021-06476-1. Epub 2022 Jan 9.


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.

Keywords: Adverse effects; Alpelisib; Dose reduction; Drug cessation; Drug discontinuation; Drug efficacy.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Female
  • Humans
  • Middle Aged
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Thiazoles
  • Triple Negative Breast Neoplasms* / drug therapy


  • Receptors, Estrogen
  • Thiazoles
  • Alpelisib
  • Receptor, ErbB-2