medwireNews: A retrospective analysis has found a significantly higher incidence of hyperglycemia among breast cancer patients treated with alpelisib in standard care than on clinical trials.
The researchers from Memorial Sloan Kettering Cancer Center in New York, USA, say that there could be several potential reasons for this difference, such as a higher proportion of patients with known diabetes in the standard care cohort, whereas “uncontrolled or insulin‐dependent diabetes and additional fasting glucose/HbA1c [glycated hemoglobin] cutoffs were often used as exclusion criteria” in the clinical trials.
Another reason could be that “hyperglycemia monitoring and management were more structured and intensive in some clinical trial protocols versus clinical practice,” they add.
As reported in Cancer, the study included 247 patients with metastatic breast cancer treated with the PI3K inhibitor at the authors’ institution between 2013 and 2021. A total of 59.5% received alpelisib as standard care, while the remaining 40.5% received it as part of a clinical trial.
Hyperglycemia of any grade occurred in 61.5% of the overall population, with events of grade 3 in 22.7% and grade 4 in 6.5%. The median time of onset was 16 days.
The incidence of hyperglycemia was significantly higher in the standard care than clinical trial group, with rates of any-grade events of 80.3% versus 34.0%. Grade 1 events occurred in a respective 10.2% and 5.0% of patients, grade 2 events in 30.6% versus 16.0%, grade 3 events in 29.3% versus 13.0%, and grade 4 events in 10.9% versus 0.0%.
Reassuringly, there was no significant difference in progression-free survival (PFS) by hyperglycemia status, “nor did PFS differ by grade of hyperglycemia, baseline BMI, or hemoglobin A1c,” say Sherry Shen and associates.
However, higher baseline HbA1c was significantly associated with the development of hyperglycemia and with the increased likelihood of dose reduction or discontinuation of alpelisib.
“[T]he identification of glycemic status as a modifiable risk factor offers the potential to mitigate this adverse effect and improve treatment delivery,” writes the team.
Two-thirds (66.4%) of the 152 patients who developed hyperglycemia received antihyperglycemic treatment, most commonly metformin (89.1%), either alone or in combination. A total of 68.3% of patients required one antihyperglycemic agent, 22.8% needed two, and 8.9% needed three or more agents.
A fifth (19.8%) of patients were referred to an endocrinologist, and this proportion also varied significantly between the standard care and clinical trial groups, at 30% and 6%, respectively.
“Our findings indicate the need for more effective strategies to mitigate PI3K inhibitor‐associated hyperglycemia,” comment Shen and colleagues.
They note that “[t]he primary mechanism of metformin action is activation of AMP‐activated protein kinase, which is abolished by PI3K inhibition, although there may be some clinical efficacy at high doses,” and thus, “newer anti‐hyperglycemia agents may be preferred.”
The investigators add that “[d]ietary strategies may also be successful adjuncts to reducing hyperglycemia and may even contribute antitumor effects.”
And they conclude: “Given the complexity of anti‐hyperglycemic treatment considerations in this setting, multidisciplinary support including consultation with dieticians and endocrinologists is warranted.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group