Researchers have uncovered elevated rates of hyperglycemia among patients who have breast cancer receiving treatment with alpelisib, according to a recent study published by Shen et al in Cancer.
Background
Alpelisib is designed to target the phosphoinositide 3-kinase (PI3K) protein, which is involved in cell growth and may contribute to the development of cancer when mutated. In 2019, the U.S. Food and Drug Administration approved the use of alpelisib in combination with the estrogen receptor antagonist fulvestrant for certain cases of metastatic breast cancer that have PIK3CA mutations.
However, targeting PI3K can cause side effects such as hyperglycemia, which may result in dehydration or kidney damage and may require hospitalization in severe instances.
Study Methods and Results
In this study, the researchers analyzed 247 cases of metastatic breast cancer treated as standard care or in clinical trials with the goal of better understanding the incidence, risk factors, and treatment patterns of alpelisib-associated hyperglycemia in this patient population.
The researchers found the rate of hyperglycemia was 80.3%, and the rate of serious hyperglycemia was 40.2% among the 147 patients treated with alpelisib as standard care compared with 34.0% and 13.0%, respectively, among the 100 patients who were treated during clinical trials. The median time to onset of hyperglycemia after initiating alpelisib was 16 days. The researchers reported that having initially elevated hemoglobin A1c levels—a biomarker of hyperglycemia in patients with prediabetes or diabetes—was a risk factor for later developing hyperglycemia.
Among the patients who developed hyperglycemia, 66.4% of them received treatment, most commonly with the diabetes agent metformin.
Conclusions
“If a patient is identified to have a PI3KCA mutation and thus eligible for treatment with alpelisib, we should be checking hemoglobin A1c levels and partnering with the patient’s primary care physician and/or endocrinologist to optimize their blood sugar levels,” suggested lead study author Sherry Shen, MD, of Memorial Sloan Kettering Cancer Center, New York. “This needs to be done months before initiating alpelisib, because once alpelisib is started, hyperglycemia usually develops within the first 2 weeks of treatment. Being preemptive about improving glycemic status and treating prediabetes/diabetes will hopefully lower the patient’s risk of developing hyperglycemia and thus lower their risk of needing to discontinue a drug that could be effective for their cancer,” she emphasized.
The researchers noted that optimizing patients’ blood sugar levels often involves changes in their dietary and exercise patterns and may require the introduction of certain drugs. “Improving metabolic risk factors through lifestyle interventions may also improve dose delivery of alpelisib, and ongoing clinical trials by our group and other groups are testing whether metabolic interventions such as the ketogenic diet or newer medications used to treat diabetes could also improve the treatment efficacy of cancer therapies that target the PI3K pathway,” concluded senior study author Neil M. Iyengar, MD, also of Memorial Sloan Kettering Cancer Center.
Disclosure: For full disclosures of the study authors, visit acsjournals.onlinelibrary.wiley.com.
