Background: HER2-positive, estrogen receptor-positive breast cancer (HER2+, ER+ BC) is a distinct disease subtype associated with inferior response to chemotherapy plus HER2-targeted therapy compared with HER2+, ER-negative BC. Bi-directional crosstalk leads to cooperation of the HER2 and ER pathways that may drive treatment resistance; thus, simultaneous co-targeting may optimize treatment impact and survival outcomes in patients with HER2+, ER+ BC. First-line (1L) treatment for patients with HER2+ metastatic BC (mBC) is pertuzumab, trastuzumab, and taxane chemotherapy. In clinical practice, dual HER2 blockade plus a fixed number of chemotherapy cycles are given as induction therapy to maximize tumor response, with subsequent HER2-targeted maintenance treatment given as a more tolerable regimen for long-term disease control. For patients whose tumors co-express ER, maintenance endocrine therapy (ET) can be added, but uptake varies due to lack of data from randomized clinical trials investigating the superiority of maintenance ET plus dual HER2 blockade versus dual HER2 blockade alone. Giredestrant, a novel oral selective ER antagonist and degrader, shows promising clinical activity and manageable safety across phase I-II trials of patients with ER+, HER2-negative BC, with therapeutic potential in those with HER2 co-expression.
Methods: This phase III, randomized, open-label, two-arm study aims to recruit 812 patients with HER2+, ER+ locally advanced (LA)/mBC into the induction phase (fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] plus a taxane) to enable 730 patients to be randomized 1:1 to the maintenance phase (giredestrant plus PH FDC SC or PH FDC SC [plus optional ET]), stratified by disease site (visceral versus non-visceral), type of LA/metastatic presentation (de novo versus recurrent), best overall response to induction therapy (partial/complete response versus stable disease), and intent to give ET (yes versus no). The primary endpoint is investigator-assessed progression-free survival. Secondary endpoints include overall survival, objective response rate, clinical benefit rate, duration of response, safety, and patient-reported outcomes.
Discussion: heredERA BC will address whether giredestrant plus dual HER2 blockade is superior to dual HER2 blockade alone, to inform the use of this combination in clinical practice for maintenance 1L treatment of patients with HER2+, ER+ LA/mBC.
Trial Registration: ClinicalTrials.gov, NCT05296798; registered on March 25, 2022. Protocol version 3.0 (November 18, 2022).
Sponsor: F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124 4070, Basel, Switzerland.
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http://dx.doi.org/10.1186/s12885-024-12179-9 | DOI Listing |
Cancer Treat Rev
December 2024
SOLTI Cancer Research Group, Barcelona, Spain; Statistics Unit, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address:
Introduction: Antibody-drug conjugates (ADCs) trastuzumab-deruxtecan (T-DXd) and sacituzumab-govitecan (SG) provided significant progression-free survival (PFS) and overall survival (OS) improvements over chemotherapy (CT) in pretreated hormone receptor-positive (HR+) and triple-negative (TN)/HER2-low metastatic breast cancer (MBC). However, no direct comparison between the two exists, nor with the more recent datopotamab-deruxtecan (Dato-DXd).
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Biosens Bioelectron
December 2024
TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan·University of Chinese Medicine, Changsha, China. Electronic address:
Compared to single-mode detection, dual-mode sensing strategies have garnered increasing attention from researchers due to their superior detection accuracy and reliability. Exosomes, as non-invasive biomarkers, hold significant potential for disease diagnosis. However, sensitive and precise detection of exosomes still presents considerable technical challenges.
View Article and Find Full Text PDFCureus
December 2024
Department of Cardiology, Victor Babeș University of Medicine and Pharmacy, Timisoara, ROU.
Background: Alpha-smooth muscle actin (αSMA) has been widely investigated in malignancies, primarily concerning its expression in cancer-associated fibroblasts (CAFs) inside the tumor stroma. Microscopic examination indicates that αSMA expression is not confined to the tumor stromal compartment but is also present in a subset of tumor cells, and this expression correlates with an enhanced invasive phenotype of malignant cells from lung, liver, or ovarian malignancies. Information on actin expression in breast cancer (BC) cells is scarce, and its influence on clinicopathological characteristics remains ambiguous due to conflicting findings in the literature.
View Article and Find Full Text PDFMedicina (B Aires)
December 2024
Departamento de Clínica Oncológica, Instituto de Oncología Ángel H. Roffo, Buenos Aires, Argentina.
Front Immunol
December 2024
Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China.
The outcome of patients with recurrent/metastatic cervical cancer (R/M CC) is poor, with a 5-year survival rate of only 10%-20%. Recent advances in immunotherapy renewed its interest in R/M CC treatment. It has been suggested that cadonilimab, a novel bispecific antibody targeting programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), significantly improved the survival outcomes of the R/M CC.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!