First Drug Targeting HER2-Mutant Non-Small Cell Lung Cancer Approved by FDA

Dr. Bob Li

Thoracic oncologist Bob Li is developing new targeted therapies for lung cancer.

On August 11, 2022, the U.S. Food and Drug Administration (FDA) approved the drug trastuzumab deruxtecan (also known as T-DXd or Enhertu®) for the treatment of advanced non-small cell lung cancer (NSCLC) driven by mutant HER2. Trastuzumab deruxtecan was previously approved for the treatment of HER2-positive breast cancer, including in patients with low levels of the HER2 protein.

An MSK-Led Study of Trastuzumab Deruxtecan Contributed to Drug Approval

In January 2022, researchers from Memorial Sloan Kettering Cancer Center (MSK) published a study in The New England Journal of Medicine (NEJM) that highlighted the benefits of trastuzumab deruxtecan for treating people with HER2-mutant NSCLC. The research was also presented at the European Society for Medical Oncology (ESMO) Congress 2021 by MSK thoracic oncologist Bob Li, Physician Ambassador to China and Asia-Pacific and Chief Scientific Officer for MSK Direct. Dr. Li was first author of the NEJM paper.

“These results are extremely promising for this group of patients who have typically been difficult to treat with other forms of treatment,” Dr. Li explained at the time. “Researchers and physicians at MSK have been studying HER2 in lung cancer for two decades, and this marks another paradigm-shifting therapeutic breakthrough for patients.”

A Different Approach to Treating HER2-Mutant NSCLC

Previous efforts in targeting HER2-mutant NSCLC had produced encouraging but inconsistent results. HER2 genetic mutations drive approximately 3% of nonsquamous NSCLC. Patients with these cancers are typically slightly younger in age, female, and never-smokers, and they often have a poor prognosis and an increased incidence of brain metastases. Although HER2 gene targeting has transformed the treatment of patients with breast and gastric cancers, until now no HER2-targeted therapies were approved for patients with NSCLC. Trastuzumab deruxtecan is a HER2 antibody-drug conjugate and works differently from other HER2-targeting drugs.

The NEJM study reported that between May 2018 and July 2020, 91 patients from North America, Europe, and Asia with previously treated HER2-mutant NSCLC were enrolled and treated with trastuzumab deruxtecan for the phase 2 DESTINY-Lung01 trial. Among the 91 patients, 50 patients had a confirmed objective response (54.9%) and nearly all patients showed disease control (92.3%) with a reduction in tumor size. This is the first antibody-drug conjugate (a type of precision medicine) for lung cancer, the first therapy targeting HER2 mutations in lung cancer, and the first HER2-targeted therapy for lung cancer to have received a Breakthrough Therapy designation from the FDA. Trastuzumab deruxtecan was approved under accelerated approval.