byl719 and Diarrhea

In a randomized, phase 3 trial, we compared alpelisib (at a dose of 300 mg per day) plus fulvestrant (at a dose of 500 mg every 28 days and once on day 15) with placebo plus fulvestrant in patients with HR-positive, HER2-negative advanced breast cancer who had received endocrine therapy previously. Patients were enrolled into two cohorts on the basis of tumor-tissue. A total of 572 patients underwent randomization, including 341 patients with confirmed tumor-tissue. Treatment with alpelisib-fulvestrant prolonged progression-free survival among patients with

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Class I Phosphatidylinositol 3-Kinases; Diarrhea; Female; Fulvestrant; Humans; Male; Middle Aged; Mutation; Progression-Free Survival; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Thiazoles

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