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Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.
View Article and Find Full Text PDFResults 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 PDFMOUNTAINEER-03 phase III study design: first-line mFOLFOX6 + tucatinib + trastuzumab for HER2+ metastatic colorectal cancer.
Future Oncol
December 2024
Department of Medical Oncology, Sorbonne Université et Hôpital Saint Antoine, Paris, France.
Patients diagnosed with metastatic colorectal cancer (mCRC) have a poor prognosis with survival ranging 2-3 years. The prevalence of human epidermal growth factor receptor 2 (HER2) amplification is approximately 3-4% in mCRC and increases up to 8% in patients with // wild-type (WT) CRC tumors. Tucatinib is a highly selective HER2-directed tyrosine kinase inhibitor that, in combination with trastuzumab, has demonstrated clinically meaningful activity in patients with chemotherapy-refractory, HER2-positive (HER2+), WT mCRC in the MOUNTAINEER trial.
View Article and Find Full Text PDFEmerging Therapies for Brain Metastases in NSCLC, Breast Cancer, and Melanoma: A Critical Review.
Curr Neurol Neurosci Rep
December 2024
Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.
Purpose Of Review: Advancements in precision medicine have shifted the treatment paradigm of brain metastases (BM) from non-small cell lung cancer (NSCLC), breast cancer, and melanoma, especially through targeted therapies focused on specific molecular drivers. These novel agents have improved outcomes by overcoming challenges posed by the blood-brain barrier (BBB) and resistance mechanisms, enabling more effective treatment of BM.
Recent Findings: In NSCLC, therapies such as osimertinib have improved efficacy in treating EGFR-mutant BM, with emerging combinations such as amivantamab and lazertinib offering promising alternatives for patients resistant to frontline therapies.
Updates in Treatment of HER2-positive Metastatic Breast Cancer.
Curr Treat Options Oncol
December 2024
Division of Hematology-Oncology, University of Massachusetts Chan Medical School - Baystate, Springfield, MA, USA.
The therapeutic landscape for HER2-positive metastatic breast cancer has exploded in the last two decades following the initial advent of trastuzumab, a monoclonal antibody. While the first line treatment has remained a combination of dual HER2 blockade with taxane chemotherapy, we now have several exciting options in the second line and beyond. The introduction of antibody-drug conjugates, in specific trastuzumab deruxtecan, has resulted in the best progression-free survival among patients with this subtype of breast cancer.
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