2026-04-17T10:12:54Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/135052025-09-30T02:07:01Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
ITALIANO, ANTOINE
author
Gambardella, Valentina
author
Accordino, Melissa
author
Bedard, Philippe
author
Cervantes, Andrés
author
Hamilton, Erika
author
Oliveira, Mafalda
author
Saura Manich, Cristina
2025-09-30T02:07:00Z
2025-09-30T02:07:00Z
2025-08-07T08:31:05Z2025-08-07T08:31:05Z2025-07
http://hdl.handle.net/11351/13505
PI3K inhibitor; Breast cancer; Hormone receptor-positiveInhibidor de PI3K; Càncer de mama; Receptor hormonal positiuInhibidor de PI3K; Cáncer de mama; Receptor hormonal positivoBackground: 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].
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
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)
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion