Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial
Copyright policy )Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial
AbstractTrastuzumab deruxtecan (T-DXd) intracranial activity has been observed in small or retrospective patient cohorts with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (mBC) and stable or active (untreated/previously treated and progressing) brain metastases (BMs). The phase 3b/4 DESTINY-Breast12 study investigated T-DXd in patients with HER2+ mBC and is, to our knowledge, the largest prospective study of T-DXd in patients with BMs in this setting. Patients (stable/active BMs (n = 263) and no BMs (n = 241)) treated with one or more prior anti-HER2–based regimens received T-DXd (5.4 mg per kg). Primary endpoints were progression-free survival (PFS; BMs cohort) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (non-BMs cohort). Additional endpoints included central nervous system (CNS) PFS, ORR, time to second progression, CNS ORR (BMs cohort), incidence of new symptomatic CNS metastases (non-BMs cohort), time to progression, duration of response, overall survival and safety (both cohorts). No formal hypothesis testing was conducted for this single-arm, open-label study. In the BMs cohort, 12-month PFS was 61.6% (95% confidence interval (CI): 54.9–67.6), and 12-month CNS PFS was 58.9% (95% CI: 51.9–65.3). In the non-BMs cohort, ORR was 62.7% (95% CI: 56.5–68.8). Grade 3 or higher adverse events occurred in 51% (BMs cohort) and 49% (non-BMs cohort) of patients. Investigator-reported interstitial lung disease/pneumonitis occurred in 16% (grade ≥3: 3%) of patients with BMs and 13% (grade ≥3: 1%) of patients without BMs. These data show substantial and durable overall and intracranial activity for T-DXd, supporting its use in previously treated patients with HER2+ mBC irrespective of stable/active baseline BMs. ClinicalTrials.gov identifier: NCT04739761.
- University College Cork Ireland
- University of Padua Italy
- Duke University United States
- KU Leuven Belgium
- Universidade Lusófona do Porto Portugal
Immunoconjugates, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, Receptor, ErbB-2, Oncologie, Medicaments antineoplàstics - Ús terapèutic, Research & Experimental Medicine, DESTINY-Breast12 study group, Antineoplastic Agents, Immunological, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos::inmunoterapia antineoplásica, Immunoconjugates/adverse effects, Prospective Studies, Human health sciences, 11 Medical and Health Sciences, EXPLORATORY ANALYSIS, CLINICAL-PRACTICE GUIDELINE, Other subheadings::Other subheadings::Other subheadings::/drug therapy, Anticossos monoclonals - Ús terapèutic, Brain Neoplasms, CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal, Middle Aged, Progression-Free Survival, trastuzumab deruxtecan, EMTANSINE T-DM1, Oncology, Medicine, Research & Experimental, ErbB-2/metabolism, Female, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento::supervivencia libre de progresión, Life Sciences & Biomedicine, Receptor, RADIOTHERAPY, RADIOSURGERY, Adult, Biochemistry & Molecular Biology, Receptor, erbB-2, Immunology, SOCIETY, Antineoplastic Agents, Brain Neoplasms/drug therapy, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome::Progression-Free Survival, Breast Neoplasms, CAPECITABINE, Sciences de la santé humaine, Article, Immunological/therapeutic use, Breast Neoplasms/drug therapy, COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales, CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antineoplastic Agents, Immunological, Humans, Immunoconjugates/therapeutic use, Aged, Trastuzumab/therapeutic use, Science & Technology, 42 Health sciences, ERBB2 protein, human, Cell Biology, 32 Biomedical and clinical sciences, Trastuzumab, EFFICACY, DS-8201A, Mama - Càncer - Tractament, Avaluació de resultats (Assistència sanitària), Brain Neoplasms/secondary, Camptothecin/analogs & derivatives, Camptothecin, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama, DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
Immunoconjugates, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, Receptor, ErbB-2, Oncologie, Medicaments antineoplàstics - Ús terapèutic, Research & Experimental Medicine, DESTINY-Breast12 study group, Antineoplastic Agents, Immunological, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos::inmunoterapia antineoplásica, Immunoconjugates/adverse effects, Prospective Studies, Human health sciences, 11 Medical and Health Sciences, EXPLORATORY ANALYSIS, CLINICAL-PRACTICE GUIDELINE, Other subheadings::Other subheadings::Other subheadings::/drug therapy, Anticossos monoclonals - Ús terapèutic, Brain Neoplasms, CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal, Middle Aged, Progression-Free Survival, trastuzumab deruxtecan, EMTANSINE T-DM1, Oncology, Medicine, Research & Experimental, ErbB-2/metabolism, Female, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento::supervivencia libre de progresión, Life Sciences & Biomedicine, Receptor, RADIOTHERAPY, RADIOSURGERY, Adult, Biochemistry & Molecular Biology, Receptor, erbB-2, Immunology, SOCIETY, Antineoplastic Agents, Brain Neoplasms/drug therapy, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome::Progression-Free Survival, Breast Neoplasms, CAPECITABINE, Sciences de la santé humaine, Article, Immunological/therapeutic use, Breast Neoplasms/drug therapy, COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales, CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antineoplastic Agents, Immunological, Humans, Immunoconjugates/therapeutic use, Aged, Trastuzumab/therapeutic use, Science & Technology, 42 Health sciences, ERBB2 protein, human, Cell Biology, 32 Biomedical and clinical sciences, Trastuzumab, EFFICACY, DS-8201A, Mama - Càncer - Tractament, Avaluació de resultats (Assistència sanitària), Brain Neoplasms/secondary, Camptothecin/analogs & derivatives, Camptothecin, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama, DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms
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