Evaluation of alpelisib-induced hyperglycemia prophylaxis and associated risk factors in PIK3CA-mutated hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer

Burnette, Sarah; Poehlein, Emily; Lee, Hui‐Jie; Force, Jeremy; Westbrook, Kelly; Moore, Heather

doi:10.1007/s10549-022-06798-8

Cited by 4 publications

(1 citation statement)

References 14 publications

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“…The inhibition of this pathway can lead to abrogated insulin function, impaired insulin secretion, and the development of insulin resistance, resulting in hyperglycemia 2,4,31 . Previous studies have reported the incidence of hyperglycemia associated with PI3K-AKT-mTOR pathway inhibitors in large phase III clinical trials ranging from 13 to 63.7% and high-grade hyperglycemia from 4 to 32.7% [32][33][34] . The incidence of hyperglycemia may also differ depending on the combination drug, disease stage, and alpelisib dose used.…”

Section: Discussionmentioning

confidence: 99%

Phase Ib and pharmacokinetics study of alpelisib, a PIK3CA inhibitor, and capecitabine in patients with advanced solid tumors

Lim

Kim

et al. 2023

Preprint

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This phase Ib study was performed to determine the safety, the maximal tolerated dose (MTD), and recommended phase II dose (RP2D) of capecitabine with alpleisib in patients with advanced solid tumors. Regardless of PIK3CA mutation, patients were administered orally once daily alpelisib (200mg and 300mg) and twice daily capecitabine (850mg/m2, 1,000mg/m2, 1,250mg/m2, days 1–14) every 3 weeks. Standard “3+3” dose escalation was used to define the MTD. The effect of alpelisib on the PK of capecitabine was assessed. Patients with 6 colorectal cancer (three PIK3CA mutation) and 6 breast cancer (all PIK3CA mutation) were enrolled. The first three patients in dose level 0 (alpelisib 200mg, capecitabine 1,000 mg/m2) had no dose-limiting toxicities (DLTs). In dose level 1 (alpelisib increased to 300 mg), one of six patients had DLT (grade 3 hyperglycemia). At dose level 2 (capecitabine 1,250 mg/m2), no patients had DLTs, establishing it as the MTD/RP2D. The most common AE was grade 1-3 hyperglycemia (75.0%). Antitumor activity was observed in patients with PIK3CA mutant breast cancer (3 partial response and 3 stable disease). Alpelisib was unaffected by capecitabine (Cmax and AUC0-12). This combination is generally tolerated, and shows antitumor activity in patients with PIK3CA mutant advanced cancers.

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Section: Discussionmentioning

confidence: 99%

Phase Ib and pharmacokinetics study of alpelisib, a PIK3CA inhibitor, and capecitabine in patients with advanced solid tumors

Lim

Kim

et al. 2023

Preprint

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show abstract

C-Peptide and BMi predict anti-hyperglycemic treatment lines in breast cancer patients treated with Alpelisib

Carrillo-Lopez,

Sebastian-Valles,

Sager La Ganga

et al. 2024

Endocrine

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Purpose Alpelisib is a PI3K (Phosphoinositide 3-kinases) inhibitor used for breast cancer which develops hyperglycemia based on its action on glucose metabolism regulation. This study aims to identify potential risk factors predicting hyperglycemia development and the need for multiple treatments for hyperglycemia in patients receiving Alpelisib. Methods Fourteen women diagnosed with metastatic hormone receptor-positive breast cancer carrying PI3K mutations who initiated treatment with Alpelisib were monitored through consultations in the Oncology and Endocrinology departments. Non-parametric ROC curves were generated to assess the need for three or more antidiabetic medications to achieve glycemic control. Results The study population had a median age of 64 years (range:48–69) with a median body mass index (BMI) of 26.6 kg/m2 (range: 22.9–29.4). Overweight was observed in 35.7% of the participants and obesity in 21.4%. Fifty percent of the participants had prediabetes, and 85.7% developed hyperglycemia requiring pharmacological treatment, although none of them needed to discontinue treatment for this reason. Baseline C-peptide levels and BMI were associated with the number of antidiabetic drugs used (Spearman’s Rho 0.553, p = 0.040; Spearman’s Rho 0.581, p = 0.030, respectively). ROC curve analysis showed and area under the curve (AUC) of 0.819 for the variable risk profile (defined as baseline C-peptide >10.5 ng/ml and BMI > 27 kg/m2), whereas AUC values were 0.556 and 0.514 for HbA1c and baseline glucose, respectively, (p = 0.012). Conclusion A joint follow-up by an Oncology department and a Diabetes Unit can prevent treatment discontinuation in patients under Alpelisib therapy. Baseline BMI and plasma C-peptide levels can predict an increased need for anti-hyperglycemic treatment.

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Alpelisib-Induced Diabetic Ketoacidosis: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System and Review of the Literature

Ziegengeist,

Elmes,

Strassels

et al. 2024

Clinical Breast Cancer

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Evaluation of alpelisib-induced hyperglycemia prophylaxis and associated risk factors in PIK3CA-mutated hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer

Cited by 4 publications

References 14 publications

Phase Ib and pharmacokinetics study of alpelisib, a PIK3CA inhibitor, and capecitabine in patients with advanced solid tumors

Phase Ib and pharmacokinetics study of alpelisib, a PIK3CA inhibitor, and capecitabine in patients with advanced solid tumors

C-Peptide and BMi predict anti-hyperglycemic treatment lines in breast cancer patients treated with Alpelisib

Alpelisib-Induced Diabetic Ketoacidosis: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System and Review of the Literature

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