Hyperglycemia rates after alpelisib therapy for metastatic breast cancer higher than observed in trials

ByMatthew Shinkle

Fact checked byMindy Valcarcel, MS

Key takeaways:

Researchers observed higher rates of hyperglycemia among patients treated with alpelisib as standard of care.
Statistical analysis showed an association between baseline HbA1c and development of hyperglycemia.

Patients with metastatic breast cancer treated with alpelisib as standard care had elevated blood glucose levels compared with those who received the drug as part of a clinical trial, according to data published in Cancer.

The results revealed that more than 80% of patients who received the drug as standard treatment for metastatic breast cancer subsequently developed some form of hyperglycemia.

Hyperglycemia rate infographic — Data derived from Shen S, et al. *Cancer.* 2023;doi:10.1002/cncr.34928.

“We were surprised to find that the rates of high blood sugar with alpelisib were greater than what had been reported in clinical trials, which may be because clinical trials typically have strict eligibility criteria and patients are monitored very closely,” Sherry Shen, MD, an oncologist at Memorial Sloan Kettering Cancer Center, told Healio. “Reassuringly, we also found that measuring hemoglobin A1c can identify people at risk for this side effect and, if done early enough, can provide a window of time to improve glycemic status before starting alpelisib.”

Sherry Shen

Background and methodology

The combination of fulvestrant and alpelisib (Piqray, Novartis) has been shown to improve PFS among patients with metastatic hormone receptor-positive PIK3CA-mutant breast cancer. The FDA approved the regimen in 2019 for postmenopausal women and men with hormone receptor-positive, HER2-negative, PIK3CA-mutated breast cancer that progressed during or after an endocrine-based regimen.

Hyperglycemia is one of the known adverse events related to use of a PI3K inhibitor, according to study investigators.

Shen and colleagues conducted a retrospective study to assess the incidence, risk factors and treatment of alpelisib-associated hyperglycemia among patients with metastatic breast cancer.

Researchers included data from 247 patients (median age, 62 years; 99.1% women; 80.1% white) who received alpelisib between 2013 and 2021 at Memorial Sloan Kettering Cancer Center, taking into account alpelisib prescription dates and patient/tumor characteristics via medical records.

Among those included in the analysis, researchers noted a baseline median body mass index of 25.4 kg/m²and median HbA1c of 5.5%.

Results

Of the 247 included patients in the study, 152 (61.5%) developed hyperglycemia, with 72 (29.2%) developing grade 3 to grade 4 hyperglycemia. Researchers observed a median time to onset of 16 days.

Meanwhile, among 100 patients who received alpelisib through a clinical trial, rates of hyperglycemia appeared significantly higher in patients treated as standard of care rather than on a clinical trial (80.3% vs. 34% for any-grade hyperglycemia; 40.2% vs. 13% for grade 3 to grade 4 hyperglycemia).

Additionally, investigators observed a significant association between baseline HbA1c and both development of hyperglycemia (P < .001) and alpelisib dose reduction or discontinuation (P = .015).

Of those who developed hyperglycemia, 101 (40.9%) received treatment, typically with metformin. A total of 49 patients received referral to an endocrinologist, which demonstrated an association with SGLT2 inhibitor prescription (P = .007).

The researchers noted study limitations, including not being able to differentiate fasting vs. nonfasting status for serum glucose levels and difficulty in drawing conclusions about the efficacy of various anti-hyperglycemic strategies.

Next steps

Due to the observed high rates of hyperglycemia among patients treated with alpelisib as standard of care, researchers recommend testing and metabolic measurements should be conducted prior to treatment with the agent.

“The most important takeaway is that genomic testing and measurement of hemoglobin A1c should be done early so that candidates for treatment with alpelisib can use their time during first-line treatment to optimize blood sugar levels through diet and exercise before starting alpelisib,” Shen told Healio.

“Testing hemoglobin A1c early could also identify undiagnosed diabetes or prediabetes, which could be treated with medications prior to starting alpelisib,” she added. “This strategy could lower the risk for having to stop or decrease the dose of alpelisib, which ultimately could improve treatment outcomes.”