Imlunestrant, an Oral Selective Estrogen Receptor Degrader, as Monotherapy and in Combination With Targeted Therapy in Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Phase Ia/Ib EMBER Study
Copyright policy )Imlunestrant, an Oral Selective Estrogen Receptor Degrader, as Monotherapy and in Combination With Targeted Therapy in Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Phase Ia/Ib EMBER Study
PURPOSE Imlunestrant is a next-generation oral selective estrogen receptor (ER) degrader designed to deliver continuous ER target inhibition, including in ESR1- mutant breast cancer. This phase Ia/b trial determined the recommended phase II dose (RP2D), safety, pharmacokinetics, and efficacy of imlunestrant, as monotherapy and in combination with targeted therapy, in ER-positive (ER+) advanced breast cancer (ABC) and endometrial endometrioid cancer. The ER+/human epidermal growth factor receptor 2–negative (HER2–) ABC experience is reported here. METHODS An i3+3 dose-escalation design was used, followed by dose expansions of imlunestrant as monotherapy or in combination with abemaciclib with or without aromatase inhibitor (AI), everolimus, or alpelisib. Imlunestrant was administered orally once daily and with the combination partner per label. RESULTS Overall, 262 patients with ER+/HER2– ABC were treated (phase Ia, n = 74; phase Ib, n = 188). Among patients who received imlunestrant monotherapy (n = 114), no dose-limiting toxicities or discontinuations occurred. At the RP2D (400 mg once daily), patients (n = 51) reported grade 1-2 nausea (39.2%), fatigue (39.2%), and diarrhea (29.4%). Patients at RP2D had received previous cyclin-dependent kinase 4/6 inhibitor (CDK4/6i; 92.2%), fulvestrant (41.2%), and chemotherapy (29.4%) for ABC and achieved a median progression-free survival (mPFS) of 7.2 months (95% CI, 3.7 to 8.3). Among patients who received imlunestrant + abemaciclib (n = 42) and imlunestrant + abemaciclib + AI (n = 43), most (69.4%) were treatment-naïve for ABC; all were CDK4/6i-naïve. Patients treated with imlunestrant + everolimus (n = 42)/alpelisib (n = 21) had received previous CDK4/6i (100%), fulvestrant (34.9%), and chemotherapy (17.5%) for ABC. No new safety signals or interactions with partnered drugs were observed. The mPFS was 19.2 months (95% CI, 13.8 to not available) for imlunestrant + abemaciclib and was not reached for imlunestrant + abemaciclib + AI. The mPFS with imlunestrant + everolimus/alpelisib was 15.9 months (95% CI, 11.3 to 19.1)/9.2 months (95% CI, 3.7 to 11.1). Antitumor activity was evident regardless of ESR1 mutation status. CONCLUSION Imlunestrant, as monotherapy or in combination with targeted therapy, had a manageable safety profile with evidence of preliminary antitumor activity in ER+/HER2– ABC.
- UNSW Sydney Australia
- KU Leuven Belgium
- Université Libre de Bruxelles Belgium
- Seoul National University Korea (Republic of)
- University of Rochester United States
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, Receptor, ErbB-2, ABEMACICLIB, Aminopyridines, Administration, Oral, ALPELISIB PLUS FULVESTRANT, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Drug Therapy::Molecular Targeted Therapy, DOUBLE-BLIND, ErbB-2, MONARCH 2, Receptors, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Medicine and Health Sciences, Molecular Targeted Therapy, Aged, 80 and over, Other subheadings::Other subheadings::Other subheadings::/drug therapy, Aromatase Inhibitors, WOMEN, 600, ORIGINAL REPORTS, Middle Aged, Progression-Free Survival, Oncology, Receptors, Estrogen, GUIDELINE, Administration, Female, Life Sciences & Biomedicine, Receptor, Oral, Adult, ESR1 MUTATIONS, Receptor, erbB-2, EXEMESTANE, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::farmacoterapia::terapia molecular selectiva, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols, 610, Breast Neoplasms, Quimioteràpia combinada, ANASTROZOLE, 3211 Oncology and carcinogenesis, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Everolimus, Aged, Science & Technology, ICTS (Institute of Clinical and Translational Sciences), Cyclin-Dependent Kinase 4, 1103 Clinical Sciences, Estrogen, Thiazoles, Mama - Càncer - Tractament, Mama - Càncer - Aspectes genètics, Benzimidazoles, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama, DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
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, Receptor, ErbB-2, ABEMACICLIB, Aminopyridines, Administration, Oral, ALPELISIB PLUS FULVESTRANT, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Drug Therapy::Molecular Targeted Therapy, DOUBLE-BLIND, ErbB-2, MONARCH 2, Receptors, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Medicine and Health Sciences, Molecular Targeted Therapy, Aged, 80 and over, Other subheadings::Other subheadings::Other subheadings::/drug therapy, Aromatase Inhibitors, WOMEN, 600, ORIGINAL REPORTS, Middle Aged, Progression-Free Survival, Oncology, Receptors, Estrogen, GUIDELINE, Administration, Female, Life Sciences & Biomedicine, Receptor, Oral, Adult, ESR1 MUTATIONS, Receptor, erbB-2, EXEMESTANE, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::farmacoterapia::terapia molecular selectiva, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols, 610, Breast Neoplasms, Quimioteràpia combinada, ANASTROZOLE, 3211 Oncology and carcinogenesis, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Everolimus, Aged, Science & Technology, ICTS (Institute of Clinical and Translational Sciences), Cyclin-Dependent Kinase 4, 1103 Clinical Sciences, Estrogen, Thiazoles, Mama - Càncer - Tractament, Mama - Càncer - Aspectes genètics, Benzimidazoles, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama, DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
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