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Results of a patient-level pooled analysis of three studies of trastuzumab deruxtecan in HER2-positive breast cancer with active brain metastasis.
ESMO Open
January 2025
Dana-Farber Cancer Institute, Boston. Electronic address:
Background: Brain metastases (BMs) are common in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer, increasing morbidity and mortality. Systemic therapy for BMs can be effective, with the triple combination of trastuzumab, capecitabine, and tucatinib being a potential standard. More recently, intracranial activity of antibody-drug conjugates has been reported, but the size of individual studies has been small.
View Article and Find Full Text PDFThe Nonclinical Safety Assessment of a Novel Anti-CEACAM5 Antibody Exatecan Conjugate Predicts a Low Risk for Interstitial Lung Disease (ILD) in Patients-The Putative Mechanism Behind ILD.
Int J Toxicol
January 2025
Chemical and Preclinical Safety Department, Global Chemical and Preclinical Safety, Merck KGaA, Darmstadt, Germany.
The therapeutic window of antibody drug-conjugates (ADC) remains challenging due to safety issues such as interstitial lung disease (ILD) observed with specific deruxtecan-based ADCs. To avoid ILD, we designed M9140 by conjugating the maleimide-containing hydrophilic β-glucuronide linker to exatecan and our anti-CEACAM5 (CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 5) specific antibody. Following repeated iv-infusion at 3 to 30 mg/kg of M9140 every 3 weeks, the pathological findings obtained in cynomolgus monkeys were confined to gastrointestinal and hematolymphoid tissues and resembled the toxicity of exatecan.
View Article and Find Full Text PDFHuman Epidermal Growth Factor Receptor 2 Positive Advanced Gastric or Esophagogastric Adenocarcinoma: Reflecting on the Past to Gain a New Insights.
Curr Oncol Rep
January 2025
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa City, Chiba, Japan.
Purpose Of Review: Human epidermal growth factor receptor 2 (HER2) is a critical target in advanced gastric cancer (AGC). This review highlights the current treatment landscape, lessons learned from past clinical trials, and prospects for future treatment strategies for HER2-positive AGC.
Recent Findings: Trastuzumab had been the standard treatment for HER2-positive AGC for a decade, and subsequently, trastuzumab deruxtecan, an antibody-drug conjugate (ADC), emerged with an impressive response.
A Comparative Analysis of the Value of HER2 Immunohistochemistry Scoring in Primary and Metastatic Breast Cancer, in the Era of HER2 "Low" Breast Cancers.
Clin Breast Cancer
December 2024
Department of Pathology, Northwell Lenox Hill Hospital, New York, NY. Electronic address:
Background: In the DESTINY-B04 trial, patients with pretreated HER2 low metastatic breast cancer (defined as immunohistochemistry score of 1+ or 2+ and negative in situ hybridization) had significant survival improvement with Trastuzumab therapy.
Methods: The goal of our study was to compare the HER2 immunohistochemistry scores of paired primary and metastatic breast cancer, with emphasis on HER2 low criteria and its implications for detailed immunohistochemistry interpretation. Using the pathology database from 2011, we identified 272 cases of primary breast cancers with paired metastases.
Efficacy and safety of antibody-drug conjugates in pretreated HER2-low metastatic breast cancer: A systematic review and network meta-analysis.
Cancer Treat Rev
January 2025
SOLTI Cancer Research Group, Barcelona, Spain; Statistics Unit, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address:
Article Synopsis
- Antibody-drug conjugates (ADCs) T-DXd and SG improved progression-free survival (PFS) and overall survival (OS) compared to chemotherapy in metastatic breast cancer (MBC) but have not been directly compared.
- A network meta-analysis revealed that T-DXd and SG had similar efficacy in hormone receptor-positive (HR+) and triple-negative (TN)/HER2-low MBC, while T-DXd showed better results against standard chemotherapy.
- T-DXd demonstrated more favorable outcomes in HR+/HER2-low for both PFS and OS, but SG showed higher rates of specific side effects, including neutropenia and diarrhea, while T-DXd was associated with more serious adverse events like pneumonitis and cardiotoxicity
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