June 17, 2024

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Antibody-drug conjugates: Significant role for non-small cell lung cancer

NEJM: Antibody-drug conjugates play a significant role in the treatment of non-small cell lung cancer with mutations in the HER2 gene

Antibody-drug conjugates: Significant role for non-small cell lung cancer.

[NEJM] Antibody-drug conjugates play a significant role in the treatment of non-small cell lung cancer with mutations in the HER2 gene.

An international clinical trial led by researchers from the Dana-Farbe Cancer Institute found that more than half of non-small cell lung cancer (NSCLC) patients with HER2 gene mutations received a combination of chemotherapy drugs and antibody drugs. , Its tumor stops growing or shrinking for a long time.

The results of the study were published yesterday at the 2021 European Society of Medical Oncology (ESMO) conference and the “The New England Journal of Medicine”. -DXd) plays an important role in the treatment of NSCLC patients with HER2 gene mutations. There is currently no approved targeted treatment for such patients.

Antibody-drug conjugates: Significant role for non-small cell lung cancer.

Approximately 3% of non-squamous NSCLC patients have HER2 mutations, and there are nearly 6,000 new cases each year in the United States. These tumors are more common in people who have never smoked than people who have smoked.

They usually have a poor prognosis and often metastasize to the brain. Although drugs targeting the HER2 protein have been successfully used to treat breast and gastric cancer, they have not yet been approved for use in NSCLC patients. Therefore, such patients are usually treated with standard chemotherapy or immunotherapy, which has limited effect on patients who have received previous treatments.

The senior author of the study, Dr. Pasi Jänne of Dana-Farber, said: “The results of the NSCLC clinical trial of travalizumab (an antibody drug that binds to the HER2 protein) combined with chemotherapy have been disappointing. Part of the reason is that it is difficult to determine which ones.

Patients may benefit from the drug, and cases of overexpression of this protein are rare. Recent studies have focused on NSCLC with mutations in the HER2 gene, rather than NSCLC with too much HER2 protein.”

In the new study, patients with metastatic HER2 gene mutation NSCLC whose cancer is resistant to standard therapies, in a second phase clinical trial called “DESTINY-Lung01”, the use of antibody drugs and chemotherapy drugs Conjugate T-DXd treatment. The conjugate is a combination of a HER2 targeting antibody and an inhibitor called topoisomerase I (topoisomerase I).

This conjugate prevents cancer cells from replicating their DNA, leading to cancer cell death. The conjugate has been approved for the treatment of breast and gastric cancers that overexpress the HER2 protein; in NSCLC, it is being used to detect cancers containing mutations in the protein.

The trial enrolled 91 patients. Among them, 54.9% of patients have an objective response to T-DXd, which means their cancer is under control or shrinking.

The reaction occurred in patients who had previously received multiple cancer treatments and whose NSCLC carried multiple different HER2 mutations.

The median duration of drug response was 9.3 months, and the median survival time before the disease began to worsen was 8.2 months. Overall, the median survival of patients who responded to the drug was 17.8 months.

The most common side effects are nausea, fatigue and hair loss. Forty-two participants were considered to have very serious or more serious drug-related side effects, the most common of which were low white blood cell counts and anemia.

Twenty-four patients developed interstitial lung disease or lung scars after treatment. Because of this problem, investigators stopped using T-DXd on 16 patients and discontinued the use of 8 patients.

Patients with this condition are treated with steroids. The ongoing Phase II trial is testing the doses of the two drugs in more patients to determine their effects on efficacy and side effects.

Jänne commented: “In this multicenter international trial, T-DXd therapy has a high response rate and long-lasting clinical benefits in patients with advanced HER2 mutant NSCLC. This proves that it has the potential to become a difficult-to-treat cancer. Targeted therapy.”

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