2026-04-13T00:07:56Zhttps://recercat.cat/oai/request

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

00925njm 22002777a 4500 dc ITALIANO, ANTOINE author Gambardella, Valentina author Accordino, Melissa author Bedard, Philippe author Cervantes, Andrés author Hamilton, Erika author Oliveira, Mafalda author Saura Manich, Cristina author 2025-08-07T08:31:05Z 2025-08-07T08:31:05Z 2025-07 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]. http://hdl.handle.net/11351/13505 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 Safety overview and management of inavolisib alone and in combination therapies in PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer (GO39374)