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Preventing alpelisib-related hyperglycaemia in HR+/HER2−/PIK3CA-mutated advanced breast cancer using metformin (METALLICA): a multicentre, open-label, single-arm, phase 2 trial

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dc.contributor.authorLlombart Cussac, Antonio
dc.contributor.authorPérez Garcia, José Manuel
dc.contributor.authorRuiz Borrego, Manuel
dc.contributor.authorTolosa, Pablo
dc.contributor.authorBlanch, Salvador
dc.contributor.authorFernández Ortega, Adela
dc.contributor.authorUrruticoechea, Ander
dc.contributor.authorBlancas, Isabel
dc.contributor.authorSaura, Cristina
dc.contributor.authorRojas, Beatriz
dc.contributor.authorBermejo, Begoña
dc.contributor.authorPonce Lorenzo, José
dc.contributor.authorGion, María
dc.contributor.authorCortez Castedo, Patricia
dc.contributor.authorLlabres, Elisenda
dc.contributor.authorGalve, Elena
dc.contributor.authorCueva, Juan Fernando
dc.contributor.authorLópez, Ana
dc.contributor.authorAlonso Romero, José Luis
dc.contributor.authorGonzález Santiago, Santiago
dc.contributor.authorMartínez de Dueñas, Eduardo
dc.contributor.authorCiruelos, Eva
dc.contributor.authorMartrat, Griselda
dc.contributor.authorGener, Petra
dc.contributor.authorAlcalá López, Daniel
dc.contributor.authorSampayo Cordero, Miguel
dc.contributor.authorGómez Peralta, Fernando
dc.contributor.authorCortés, Javier
dc.contributor.departmentMedicina
dc.date.accessioned2024-11-05T11:56:23Z
dc.date.available2024-11-05T11:56:23Z
dc.date.issued2024-05
dc.description© 2024. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Published version of a Published Work that appeared in final form in EClinicalMedicine. To access the final edited and published work see https://doi.org/10.1016/j.eclinm.2024.102520
dc.description.abstractBackground 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. In the full analysis set, median PFS was 7.3 months (95% CI: 5.9–not reached), ORR was 20.6% (95% CI: 11.7–32.1%), and CBR was 52.9% (95% CI: 40.4–65.2). Interpretation In HR+/HER2−/PIK3CA-mutated ABC, prophylactic metformin before alpelisib plus endocrine treatment has low incidence and severity of alpelicib-induced hyperglycaemia.es
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dc.format.extent10es
dc.identifier.citationeClinicalMedicine, 2024, Vol. 71 : 102520
dc.identifier.doihttps://doi.org/10.1016/j.eclinm.2024.102520
dc.identifier.issnElectronic: 2589-5370
dc.identifier.urihttp://hdl.handle.net/10201/146006
dc.languageenges
dc.publisherElsevier
dc.relationNovartis Pharmaceuticalses
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S2589537024000993?via%3Dihub
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAlpelisibes
dc.subjectHyperglycaemiaes
dc.subjectProphylactic metformines
dc.subjectHR+/HER2−/PIK3CA-mutated advanced breast canceres
dc.titlePreventing alpelisib-related hyperglycaemia in HR+/HER2−/PIK3CA-mutated advanced breast cancer using metformin (METALLICA): a multicentre, open-label, single-arm, phase 2 triales
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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