Academic Journal
Preventing alpelisib-related hyperglycaemia in HR+/HER2−/PIK3CA-mutated advanced breast cancer using metformin (METALLICA): a multicentre, open-label, single-arm, phase 2 trialResearch in context
| العنوان: | Preventing alpelisib-related hyperglycaemia in HR+/HER2−/PIK3CA-mutated advanced breast cancer using metformin (METALLICA): a multicentre, open-label, single-arm, phase 2 trialResearch in context |
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| المؤلفون: | Antonio Llombart-Cussac, José Manuel Pérez-Garcia, Manuel Ruiz Borrego, Pablo Tolosa, Salvador Blanch, Adela Fernández-Ortega, Ander Urruticoechea, Isabel Blancas, Cristina Saura, Beatriz Rojas, Begoña Bermejo, José Ponce Lorenzo, María Gion, Patricia Cortez-Castedo, Elisenda Llabres, Elena Galve, Juan Fernando Cueva, Ana López, José Luis Alonso-Romero, Santiago González-Santiago, Eduardo Martínez de Dueñas, Eva Ciruelos, Griselda Martrat, Petra Gener, Daniel Alcalá-López, Miguel Sampayo-Cordero, Fernando Gómez-Peralta, Javier Cortés |
| المصدر: | EClinicalMedicine, Vol 71, Iss , Pp 102520- (2024) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2024 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Alpelisib, Hyperglycaemia, Prophylactic metformin, HR+/HER2−/PIK3CA-mutated advanced breast cancer, Medicine (General), R5-920 |
| الوصف: | Summary: Background: Hyperglycaemia is an early and frequent adverse event during alpelisib treatment. METALLICA aimed to evaluate prophylactic metformin to prevent or reduce hyperglycaemia occurrence in patients with HR+/HER2−/PIK3CA-mutated advanced breast cancer (ABC). Methods: Between August 13th, 2020 and March 23rd, 2022, this 2-cohort, phase 2, multicentre, single-arm trial (NCT04300790) enrolled patients with HR+/HER2−/PIK3CA-mutated ABC: cohort A, normal glycaemia (fasting plasma glucose <100 mg/dL [<5.6 mmol/L] and HbA1c <5.7%), and cohort B, prediabetes (fasting plasma glucose 100–140 mg/dL [5.6–7.8 mmol/L] and/or haemoglobin A1C [HbA1c] 5.7–6.4%). Participants were at least 18 years old, with Eastern Cooperative Oncology Group performance status of 0–1, and up to two prior lines of endocrine therapy (ET) for ABC. Alpelisib plus ET were administered in 28-day cycles after initiation of prophylactic metformin plus ET. Primary endpoint was the incidence of grade 3–4 hyperglycaemia over the first 8 weeks. Secondary endpoints included safety, progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). The primary objective for cohort A and B is met with ≤7 (14.6%) and ≤4 (20%) patients with grade 3–4 hyperglycaemia over the first 8 weeks, respectively. Findings: 233 patients were screened, and 68 (20.2%) patients were enrolled in cohorts A (n = 48) and B (n = 20). Median follow-up was 7.8 months (IQR 1.4–19.6). Over the first 8 weeks, one (2.1%) of 48 patients in cohort A (95% CI: 0.5–11.1; P < 0.0001), and three (15.0%) of 20 patients in cohort B (95% CI: 5.6–37.8; P = 0.016) had grade 3–4 hyperglycaemia. Serious treatment-related adverse events occurred in seven patients (10.3%). The most common were rash (two [2.9%]), vomiting (two [2.9%]), and diarrhoea (two [2.9%]). Discontinuation of alpelisib caused by AEs was reported in nine patients (13.2%), none caused by hyperglycaemia. At data cutoff (15 June, 2022), no treatment-related deaths were observed. ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2589-5370 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2589537024000993; https://doaj.org/toc/2589-5370; https://doaj.org/article/c5ba8bd9a6864624b463e00529accd71 |
| DOI: | 10.1016/j.eclinm.2024.102520 |
| الاتاحة: | https://doi.org/10.1016/j.eclinm.2024.102520 https://doaj.org/article/c5ba8bd9a6864624b463e00529accd71 |
| رقم الانضمام: | edsbas.849A436E |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 25895370 |
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| DOI: | 10.1016/j.eclinm.2024.102520 |