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oai:recercat.cat:11351/135052025-09-30T02:07:01Zcom_2072_378070com_2072_378040col_2072_378092

Safety overview and management of inavolisib alone and in combination therapies in PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer (GO39374) ITALIANO, ANTOINE Gambardella, Valentina Accordino, Melissa Bedard, Philippe Cervantes, Andrés Hamilton, Erika Oliveira, Mafalda Saura Manich, Cristina Institut Català de la Salut [Gambardella V, Cervantes A] Hospital Clínico de Valencia, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain. [Accordino MK] Columbia University Irving Medical Center, New York, USA. [Bedard PL] Princess Margaret Cancer Centre – University Health Network, University of Toronto, Toronto, Canada. [Hamilton E] Sarah Cannon Research Institute, Nashville, USA. [Italiano A] Department of Medicine, Institut Bergonié, Bordeaux, France. Faculty of Medicine, University of Bordeaux, Bordeaux, France. [Oliveira M, Saura C] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Anomalies cromosòmiques Enzims - Inhibidors - Ús terapèutic Enzims - Inhibidors - Ús terapèutic Quimioteràpia combinada Mama - Càncer - Tractament PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Phosphatidylinositol 3-Kinases Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::transferasas::fosfotransferasas::fosfotransferasas (grupo alcohol aceptor)::fosfatidil inositol 3 cinasas Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores PI3K inhibitor; Breast cancer; Hormone receptor-positive Inhibidor de PI3K; Càncer de mama; Receptor hormonal positiu Inhibidor de PI3K; Cáncer de mama; Receptor hormonal positivo Background: Inavolisib is a potent and selective PI3Kα inhibitor that promotes degradation of mutated p110α. We report safety from a phase I/Ib dose-escalation/-expansion study (GO39374; NCT03006172) of inavolisib alone or in combination therapies in PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative advanced breast cancer. Patients and methods: Patients received inavolisib [oral once daily (od)] alone, with letrozole (2.5 mg od) or fulvestrant (500 mg intramuscularly 4 weekly) ± palbociclib (125 mg od for 21/28 days); metformin was included in one arm. Primary endpoint: safety and tolerability. Results: At data cutoff (1 January 2024), 190 patients had been treated, of which 179 (94.2%) had discontinued study treatment, mainly due to progressive disease [146 (76.8%)]. Treatment-related any-grade and grade 3-5 adverse events (AEs) occurred in 181 (95.3%) and 107 (56.3%) patients, respectively. Inavolisib-related AEs led to inavolisib withdrawal in 5 (2.6%) and dose reductions/interruptions in 103 (54.2%) patients. Hyperglycemia, diarrhea, stomatitis (grouped terms), and rash (grouped terms) occurred in 129 (67.9%), 124 (65.3%), 93 (48.9%), and 47 (24.7%) patients, respectively. Hyperglycemia, diarrhea, and stomatitis mainly occurred early in treatment, and were manageable with supportive measures (including oral antihyperglycemic agents, common antidiarrheal medications, and dexamethasone mouthwash, respectively) and/or inavolisib dose modifications (dose interruptions with or without dose reductions). Hyperglycemia remained frequent in patients with risk factors, despite early metformin treatment. Rash was mostly grade 1 and required no treatment. Patients treated for ≥1 year [n = 65 (34.2%)] demonstrated encouraging long-term tolerability. Conclusions: Inavolisib alone or in combination with HR-positive breast cancer therapies demonstrated a manageable safety and tolerability profile, which supports its ongoing development. This work was supported by Genentech, Inc., South San Francisco, CA; and the Memorial Sloan Kettering Cancer Center [support grant number P30 CA008748]. 2025-08-07T08:31:05Z 2025-08-07T08:31:05Z 2025-07 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Gambardella V, Accordino MK, Bedard PL, Cervantes A, Hamilton E, Italiano A, et al. Safety overview and management of inavolisib alone and in combination therapies in PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer (GO39374). ESMO Open. 2025 Jul;10(7):105303. 2059-7029 http://hdl.handle.net/11351/13505 10.1016/j.esmoop.2025.105303 40513140 001511060900002 http://hdl.handle.net/11351/13505 eng ESMO Open;10(7) https://doi.org/10.1016/j.esmoop.2025.105303 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf Elsevier Scientia