Trastuzumab Deruxtecan Is Active in HER2-Mutant NSCLC

HER2 mutations drive roughly 3% of nonsquamous non–small-cell lung cancers (NSCLC) and are often seen in patients who are slightly younger, female, and never-smokers. This subtype also carries a poor prognosis and an increased incidence of brain metastasis. These patients typically receive standard chemotherapy and/or immunotherapy.

Trastuzumab deruxtecan is a HER2 antibody–drug conjugate. In the DESTINY-Lung01 trial, investigators assessed the efficacy and safety of trastuzumab deruxtecan in 91 patients with HER2-mutant NSCLC who had relapsed on or were refractory to standard therapy. Centrally confirmed objective response occurred in 55% of the patients (95% CI, 44–65). A disease control rate of 92.3% was observed, with a decrease in tumor size in most patients. The median duration of response was 9.3 months (95% CI, 5.7–14.7). Median progression-free survival was 8.2 months (95% CI, 6.0–11.9), and median overall survival was 17.8 months (95% CI, 13.8–22.1).

The safety profile was generally consistent with those from previous studies: grade 3 or higher drug-related adverse events occurred in 46% of patients, most commonly neutropenia (in 19%). Drug-related interstitial lung disease (ILD) or pneumonitis occurred in 26.4% but was grade 1/2 in most. Four patients developed grade 3 lung injury, and two died from ILD.