byl719 and Hyperglycemia

SOLAR-1 investigated alpelisib-fulvestrant (ALP + FLV) in patients with HR + /HER2-, PIK3CA-mutated advanced breast cancer and demonstrated a clinically significant increase in all-grade and grade (G) 3-4 hyperglycemia (HG) compared to placebo-fulvestrant. Given high rates of HG, a preventative protocol and identification of associated risk factors was implemented.. This single-center, retrospective study included patients receiving ALP + FLV. One week before ALP initiation, patients started an insulin-sensitizer. Patients had fasting plasma glucose (FPG) levels drawn day 8, 15, 28, then monthly. Primary outcome was incidence of G2-4 HG by day 28. Risk factors assessed included age, BMI, FPG, and HbA1c. Number of risk factors were compared between patients with and without HG.. Sixteen women were included with median age of 59 years. The cohort was 69% White, 25% Black, 75% with BMI ≥ 25 kg/m. Implementation of a HG prophylaxis protocol with ALP in a single-center study demonstrated fewer G3-4 HG events compared to that seen in SOLAR-1 (19% vs 36.6%). An increase in HG-associated risk factors correlated with a higher incidence of G2-4 HG.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Class I Phosphatidylinositol 3-Kinases; EGF Family of Proteins; Female; Fulvestrant; Humans; Hyperglycemia; Middle Aged; Receptor, ErbB-2; Retrospective Studies; Risk Factors

Hyperglycemia is recognized as a common adverse event for patients receiving alpelisib but has been little studied outside of clinical trials. We report the frequency of alpelisib-associated hyperglycemia in a real-world setting and evaluate proposed risk factors.. We retrospectively identified patients with PIK3CA-mutated, hormone receptor-positive, metastatic breast cancer who initiated treatment with alpelisib plus fulvestrant between August 2019 and December 2021. Ordinal logistic regression evaluated 5 characteristics (diabetes, prediabetes, body mass index [BMI], age, and Asian ancestry) as independent risk factors for ALP-associated hyperglycemia grades 2-4. Risk of error from multiple hypothesis testing was controlled using the false discovery rate method.. The study included n = 92 subjects, all but 1 female, mean age 59.9 (+11.9) years with 50% non-Hispanic White, 15% Hispanic/Latino, 13% Asian, 9% African/Black, and 13% other/unknown. In total 34% of patients had diabetes, 10% had pre-diabetes, and 56% had normoglycemia. Thirty-six percent were obese, 32% were overweight, 25% were normal weight, and 7% were lean. Frequency of grades 1-4 hyperglycemia in current subjects (64.1%) was similar to hyperglycemia reported in the SOLAR-1 trial (63.7%). Our subjects' risk of grades 2-4 hyperglycemia was independently increased by pre-existing diabetes (Odds ratio 3.75, 95% CI, 1.40-10.01), pre-diabetes (6.22, 1.12-34.47), Asian ancestry (7.10, 1.75-28.84), and each unit of BMI above 20 (1.17, 1.07-1.28).. While receiving alpelisib, patients of Asian ancestry, as well as patients with pre-existing hyperglycemia and/or BMI above 20, should be closely monitored for hyperglycemia. The mechanism underlying the current association of alpelisib-associated hyperglycemia with Asian ancestry is independent of BMI and merits further study. The high incidence of hyperglycemia resulted in a change in practice to include consultation with a diabetes nurse educator or endocrinologist at the start of alpelisib.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Fulvestrant; Humans; Hyperglycemia; Middle Aged; Prediabetic State; Receptor, ErbB-2; Retrospective Studies

To explore and describe the adverse reaction signals in the safety reporting for alpelisib.. We performed a disproportionality analysis of the World Health Organization's VigiBase pharmacovigilance database from 1 January 2019 to 30 June 2021. Disproportionality analysis by information components (ICs) were used to evaluate the potential association between adverse events (AEs) and alpelisib.. A total of 33 327 reports were extracted, 5695 of them were chosen with alpelisib as the suspected drug. After combining the same ID, 687 cases remained. The 45-64-years group had the most cases (n = 203, 29.55%). There were 129 Preferred Terms with significant signals. Hyperglycaemia (IC025 = 6.74), breast cancer metastatic (IC025 = 5.85) and metastases to liver (IC025 = 4.70) were the AEs with the strongest signal. AEs with the most cases were hyperglycaemia (n = 595), rash (n = 535) and diarrhoea (n = 475).. We established a comprehensive list of AEs potentially associated with alpelisib. AEs with the most significant signals were hyperglycaemia, breast cancer metastatic, metastases to liver. The AEs with the most cases were hyperglycaemia, rash, diarrhoea, blood glucose increase and nausea.

Topics: Adverse Drug Reaction Reporting Systems; Breast Neoplasms; Databases, Factual; Diarrhea; Drug-Related Side Effects and Adverse Reactions; Exanthema; Female; Humans; Hyperglycemia; Pharmacovigilance; Thiazoles; World Health Organization

Published trials of alpelisib + fulvestrant demonstrate efficacy and high rates of adverse effects as a first-line treatment option for metastatic breast cancer and as an option after cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i). The purpose of this analysis is to determine the real-world efficacy and safety of this regimen in heavily pretreated patients. This is a retrospective cohort analysis evaluating patients receiving alpelisib + fulvestrant for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer who previously received ≤ 2 lines of therapy in the metastatic setting and those who previously received ≥ 3 lines of therapy in the metastatic setting. Adverse effects, specifically hyperglycemia, rash, and diarrhea, were reported for the entire population. Thirty-three patients were included in this analysis. Progression-free survival (PFS), overall survival, time to change in therapy, and time to discontinuation were similar in the two groups. Forty-nine percent of patients discontinued alpelisib + fulvestrant due to progression of disease, and 27% of patients discontinued treatment due to adverse effects. Hyperglycemia, rash, and diarrhea occurred at high rates: 66.7%, 45.5%, and 72.7%, respectively. All three of these adverse effects required hospitalizations and pharmacological treatment. This analysis demonstrates that the outcomes of alpelisib + fulvestrant were worse in the real-world salvage setting in HR+, HER2- metastatic breast cancer as compared to the front-line setting. The real-world tolerability of this regimen is still of great concern.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Diarrhea; Exanthema; Female; Fulvestrant; Humans; Hyperglycemia; Retrospective Studies

Topics: Diabetes Mellitus; Diabetic Ketoacidosis; Humans; Hyperglycemia; Thiazoles

The PIK3 kinase inhibitor, alpelisib, is a new breast cancer drug that can cause hyperglycemia, which can be especially severe in older patients. Yet, to our knowledge, no prior studies have sought to understand what older patients experience with alpelisib-induced hyperglycemia.. The medical records of patients who were 65 years of age or older at the initiation of alpelisib and who developed hyperglycemia were reviewed in detail; direct verbiage on hyperglycemia were extracted and reviewed with rigorous qualitative methods.. Thirty-four women with a median age of 72 (range: 65, 85) are the subject of this report; twelve had been started on insulin, four had been hospitalized for hyperglycemia, and eleven appeared to stop alpelisib because of hyperglycemia. Qualitative analyses revealed two themes. The first was patient burden, which emanated from patients' having to self-monitor glucose levels ("Monitors blood glucose (BG) 4 times daily"); taking extra medications ("Taking Jardiance 10 mg daily and Pioglitazone 15 mg daily"); frequent changes in insulin dosing ("Her insulin… was then increased…."); and frequent changes in dosing of alpelisib to help control the hyperglycemia ("Instructed to hold Piqray …."), and which also emanated from greater engagement with the healthcare system ("She was hospitalized for hyperglycemia"). The second theme focused on symptomatology and how patients suffered from hyperglycemia ("She presents to the emergency department with pre-syncope and vertigo").. Oncologists should assess older patients for the requisite abilities and resources for managing alpelisib-induced hyperglycemia in the event it occurs.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Humans; Hyperglycemia; Thiazoles

Topics: Aged; Antineoplastic Agents, Hormonal; Blood Glucose; Blood Glucose Self-Monitoring; Breast Neoplasms; Class I Phosphatidylinositol 3-Kinases; Female; Fulvestrant; Humans; Hyperglycemia; Monitoring, Ambulatory; Phosphoinositide-3 Kinase Inhibitors; Prediabetic State; Thiazoles