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Hyperglycemia and rash are expected but challenging adverse events of phosphatidylinositol-3-kinase inhibition (such as with alpelisib). Two modified Delphi panels were conducted to provide consensus recommendations for managing hyperglycemia and rash in patients taking alpelisib. Experts rated the appropriateness of interventions on a 1-to-9 scale; median scores and dispersion were used to classify the levels of agreement. Per the hyperglycemia panel, it is appropriate to start alpelisib in patients with HbA1c 6.5% (diabetes) to <8%, or at highest risk for developing hyperglycemia, if they have a pre-treatment endocrinology consult. Recommend prophylactic metformin in patients with baseline HbA1c 5.7% to 6.4%. Metformin is the preferred first-line anti-hyperglycemic agent. Per the rash panel, initiate prophylactic nonsedating H1 antihistamines in patients starting alpelisib. Nonsedating H1 antihistamines and topical steroids are the preferred initial management for rash. In addition to clinical trial evidence, these recommendations will help address gaps encountered in clinical practice.
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http://dx.doi.org/10.1038/s41523-024-00613-x | DOI Listing |
J Clin Oncol
August 2025
Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD.
Purpose: The US Food and Drug Administration (FDA) approved inavolisib with palbociclib and fulvestrant for adults with endocrine-resistant, -mutated, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer (MBC), as detected by an FDA-approved test, FoundationOne Liquid CDx assay, after recurrence on or after completing adjuvant endocrine therapy.
Patients And Methods: Approval was based on INAVO120, a randomized, double-blind, placebo-controlled trial in 325 patients with endocrine-resistant, -mutated, hormone receptor-positive, HER2-negative, locally advanced or MBC. Patients were randomly assigned (1:1) to either inavolisib (n = 161) or placebo (n = 164) in combination with palbociclib and fulvestrant.
Cureus
July 2025
Internal Medicine, Jersey Shore University Medical Center, Neptune, USA.
This case highlights a rare presentation of measles in an unvaccinated adult male in New Jersey, emphasizing the risks posed by declining vaccination rates. The outbreak linked to this case illustrates the public health dangers of vaccine hesitancy and insufficient immunization coverage. A 32-year-old male presented with five days of worsening fever, nausea, vomiting, diarrhea, and a spreading maculopapular rash.
View Article and Find Full Text PDFEur J Pediatr
August 2025
Department of Pediatric Pulmonology, Ege University Faculty of Medicine, İzmir, Turkey.
Postinfectious bronchiolitis obliterans (PIBO) is a severe chronic pulmonary disorder in children, characterized by irreversible airway obstruction following acute lower respiratory tract infections. Currently, there is no consensus on the treatment protocol for PIBO. This study aimed to evaluate the safety and effectiveness of combining intravenous pulse methylprednisolone (IVPM) with intravenous immunoglobulin (IVIG) in pediatric patients with PIBO.
View Article and Find Full Text PDFClin Transl Sci
July 2025
Clinical Pharmacology and Quantitative Pharmacology, BioPharmaceuticals R&D, AstraZeneca, Waltham, Massachusetts, USA.
Capivasertib is a potent, selective pan-AKT inhibitor. In the Phase III CAPItello-291 trial in patients with aromatase inhibitor-resistant, hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, the addition of capivasertib (400 mg twice daily, 4 days on, 3 days off) to fulvestrant significantly improved the dual primary endpoints of progression-free survival in the overall and PIK3CA/AKT1/PTEN-altered population compared with placebo plus fulvestrant and had an acceptable safety profile. Based on data from six Phase I-III trials (N = 851), a three-compartment population pharmacokinetic model was used to generate individual Bayes' capivasertib steady-state exposure parameters (AUC, C, and C).
View Article and Find Full Text PDFFront Oncol
June 2025
Department of Breast and Thyroid Surgery, Shenzhen Nanshan People's Hospital, Shenzhen, Guangdong, China.
Objectives: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of combination of Phosphatidylinositol 3-kinase (PI3K) inhibitors and fulvestrant in patients with advanced breast cancer (ABC) who are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-).
Methods: A systematic search was conducted across the PubMed, Cochrane Library, EMBASE databases and major conference websites (ASCO, ESMO, SABCS) to identify randomized controlled trials (RCTs) evaluating the combination of PI3K inhibitors and fulvestrant in the treatment of advanced breast cancer. Two independent reviewers systematically screened the literature, extracted data, and assessed the risk of bias for the included studies based on predefined criteria.