Antibody-drug conjugate shows impressive activity in patients with non-small cell lung cancer with mutation in HER2 gene


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More than half of patients with non-small cell lung cancer (NSCLC) HER2 In an international clinical trial led by researchers at the Dana-Farber Cancer Institute, the gene stopped or reduced tumor growth after treating a chemotherapeutic agent with a drug that binds to a highly targeted antibody.

Results are available today at the European Society for Medical Oncology (ESMO) 2021 and New England Journal of MedicinePoint out the important role of drag, Trastuzumab deruxtecan, in patients with this form of NSCLC, no targeted therapy is currently approved.

Mutations in about 3% of non-squamous NSCLC HER2 (Also known as ERBB2) – The United States accounts for about 6,000 new cases each year. These tumors are more common in people who have never smoked than in people who have smoked, generally have a poorer prognosis, and often metastasize to the brain. Drugs that target the HER2 protein have been successfully used to treat breast and gastric cancer due to protein oversupply, but have not been approved for patients with NSCLC. Therefore, such patients are generally treated with standard chemotherapy or immunotherapy, which has limited effect in patients who have already received previous treatment.

“Clinical trials of trastuzumab, an antibody drug that binds to the HER2 protein, in combination with chemotherapy gave disappointing results in NSCLC, which identifies patients who may benefit from the drug. Is difficult and the protein is overexpressed. ” “Recent studies have focused on NSCLC with mutations. HER2 Gene, not excess of HER2 protein. Efforts to treat such cancers with targeted therapies were encouraging, but inconsistent. “

In a new study, metastatic patients HER2-Variant NSCLC, whose cancer has become resistant to standard treatment, was treated with the antibody-drug conjugate trastuzumab delkistecan in a phase II clinical trial named DESTINY-Lung01. Conjugates are composed of HER2-targeted antibodies that bind to a drug known as a topoisomerase I inhibitor, which prevents cancer cells from copying DNA and leads to death. As a unit, the agent packs not only punch but also precision. Conjugates are approved for the treatment of breast and gastric cancers that overexpress the HER2 protein. NSCLC uses variants of the protein to test for cancer.

91 patients were enrolled in the study. More than half of them (54.9%) responded objectively to trastuzumab delxtecan. This means that the cancer has been suppressed or reduced.Responses occurred in patients who received a variety of previous cancer treatments and whose NSCLC had a variety of different mutations HER2.. The median response time to the drug was 9.3 months, and the median survival time before the disease began to worsen was 8.2 months. Overall, the median survival time for those who responded to this drug was 17.8 months.

The most common side effects were nausea, malaise and hair loss. Forty-two participants had drug-related side effects that were considered more severe. The most common of these were decreased white blood cell counts and anemia.

Twenty-four patients developed interstitial lung disease or lung scarring as a result of treatment. Researchers discontinued trastuzumab deruxtecan in 16 patients and discontinued its use in 8 patients because of this problem. Patients experiencing this condition were treated with steroids. An ongoing Phase 2 study is examining two doses of the drug in a larger patient population to determine its impact on both efficacy and side effects.

“In this multicenter international trial, treatment with trastuzumab delxtecan showed high response rates and lasting clinical benefits in advanced patients. HER2-Mutant NSCLC, “commented Jenne. “It shows clear potential as a targeted therapy for this difficult treatment. cancer.. ”

HER2-targeted antibody drugs improve progression-free survival in women with fatal forms of advanced breast cancer

For more information:
Bob T. Li et al, Trastuzumab delxtecan in HER2 mutant non-small cell lung cancer, New England Journal of Medicine (2021). DOI: 10.1056 / NEJMoa2112431

Quote: The antibody-drug conjugate has a mutation in the HER2 gene (September 19, 2021) obtained from on September 19, 2021. Shows impressive activity in patients with small cell lung cancer-conjugate-patients-non-small-cell.html

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