2026-04-14T05:05:50Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/138882025-10-24T02:03:48Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Ruiz , Manuel author Vaklavas, Christos author Baird, Richard author BERMEJO, BEGOÑA author Moreno, Irene author Oliveira, Mafalda author 2025-10-20T10:25:49Z 2025-10-20T10:25:49Z 2025-10-15 Camizestrant; CDK4/6 inhibitors; Advanced breast cancer Camizestrant; Inhibidors de CDK4/6; Càncer de mama avançat Camizestrant; Inhibidores de CDK4/6; Cáncer de mama avanzado Purpose: This trial investigated the safety and tolerability of camizestrant with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in women with estrogen receptor-positive, HER2- advanced breast cancer. Patients and methods: SERENA-1 (NCT03616587) is a phase I, multipart, open-label study in women with refractory estrogen receptor-positive, HER2- advanced breast cancer. Patients received oral once-daily camizestrant 75 or 150 mg plus abemaciclib; camizestrant 75, 150, or 300 mg plus palbociclib; or camizestrant 75 mg plus ribociclib 400 or 600 mg. Safety/tolerability, pharmacokinetics, efficacy, and impact on estrogen receptor 1 mutation ctDNA were assessed. Results: By September 16, 2024 (data cutoff), 53 patients had received camizestrant plus abemaciclib, 78 camizestrant plus palbociclib, and 60 camizestrant plus ribociclib. Patients had a median of 2 (range, 0-7) prior regimens for advanced disease; 83% had received a prior CDK4/6i and 59% prior fulvestrant. The most common treatment-emergent adverse events for camizestrant 75 mg (phase III dose) plus each CDK4/6i were diarrhea [with abemaciclib (87.5%)] and neutropenia [with palbociclib (80%) and ribociclib (32.1% for 400 mg and 53.1% for 600 mg)]. The median camizestrant tmax was ∼4 hours postdose across combinations, with an estimated half-life of 9.5 to 17 hours. No clinically meaningful drug-drug interactions were evident. In this heavily pretreated population, CBR24 was 49.5% and the median progression-free survival was 7.4 months (95% confidence interval, 5.3-9.3), with antitumor activity across all combinations, including patients previously treated with CDK4/6i and/or fulvestrant, with or without estrogen receptor 1 mutation. Conclusions: Camizestrant is well tolerated, with antitumor activity in combination with CDK4/6i. These results support the evaluation of camizestrant 75 mg plus standard CDK4/6i doses in phase III trials. Medicaments antineoplàstics - Ús terapèutic Quimioteràpia combinada Proteïnes quinases - Inhibidors - Ús terapèutic Posologia DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors Other subheadings::Other subheadings::Other subheadings::/administration & dosage ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas Otros calificadores::Otros calificadores::Otros calificadores::/administración & dosificación Camizestrant in Combination with Three Globally Approved CDK4/6 Inhibitors in Women with ER+, HER2- Advanced Breast Cancer: Results from SERENA-1