New Targeted Therapy for Lung Cancer  

The FDA granted accelerated approval to the first HER2-targeted therapy for the treatment of non-small cell lung cancer with activating HER2 mutations 

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of certain adult patients with non-small cell lung cancers (NSCLC) harboring activating mutations in HER2, as detected by an FDA-approved test.  

Fam-trastuzumab deruxtecan-nxki is a type of therapy called an antibody-drug conjugate (ADC), which consists of an anticancer drug (in this case, deruxtecan-nxki) conjugated to an antibody that specifically targets a protein found on tumor cells (in this case, fam-trastuzumab that targets HER2). Binding of the antibody portion to HER2 on the cell surface causes the cell to internalize the ADC and release its cancer-killing activity.  

Image by Librepath via Wikimedia.

Activating mutations in HER2 trigger uncontrolled cell proliferation. These types of HER2 mutations are found in approximately 2 to 4 percent of NSCLC patients. Fam-trastuzumab deruxtecan-nxki is the first HER2-directed therapy approved for HER2-mutant NSCLC. 

The accelerated approval was based on the results of the multicenter, multicohort, randomized, blinded phase II DESTINY-Lung02 clinical trial that assessed two doses of fam-trastuzumab deruxtecan-nxki in patients with unresectable or metastatic HER2-mutant NSCLC who experienced disease progression after at least one prior anticancer therapy. 

Among the 52 patients who received the approved recommended dose, the objective response rate was 58 percent, and the median duration of response was 8.7 months.  

Lung cancer is the leading cause of cancer death in the U.S. and worldwide. NSCLC accounts for more than 80 percent of all lung cancers. It is estimated that 236,740 new cases of lung and bronchus cancer will be diagnosed in the U.S. in 2022.   

The approval was rendered on August 11, 2022. Accelerated approval means continued approval may be contingent upon a confirmatory trial.