Dr Rodriguez on the Use of HER2-Directed Therapies in NSCLC

Estelamari Rodriguez, MD, MPH, associate director, Community Outreach – Thoracic Oncology, coleader, Thoracic Site Disease Group, assistant director, Diversity, Equity, and Inclusion, Sylvester Comprehensive Cancer Center, discusses adverse effects (AEs) to consider when using HER2-directed antibody-drug conjugates (ADCs) in patients with non–small cell lung cancer (NSCLC), as well as AE management strategies for patients receiving these agents.

At the 21st Annual Winter Lung Cancer Conference, Rodriguez and colleagues participated in a discussion about HER2 mutations in lung cancer. Although these mutations are relatively rare in lung cancer, fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) was approved by the FDA in 2022 for patients with HER2-mutant NSCLC, Rodriguez says. Additionally, emerging phase 1 and phase 2 data are demonstrating the utility of other HER2-directed agents in this disease, Rodriguez notes.

Although ADCs are an effective class of drugs, they are associated with AEs that resemble those patients experience when receiving chemotherapy, Rodriguez explains. Other HER2-directed drug classes, such as TKIs, are in development for patients with HER2-mutant NSCLC and may provide alternative treatment options for this patient population, Rodriguez notes. At the meeting, Rodriguez and colleagues discussed AE management for patients receiving T-DXd, who tend to be younger and have central nervous system (CNS) metastases, as T-DXd penetrates the CNS and can control brain metastases.

Patients may experience nausea when receiving T-DXd; Rodriguez and colleagues note that this AE can be managed with anti-emetics. One serious but rare AE associated with T-DXd is interstitial lung disease (ILD), Rodriguez emphasizes. Community oncologists should be aware of and watch for the warning signs of ILD in patients receiving T-DXd, which include shortness of breath, Rodriguez says. Furthermore, early treatment of ILD often depends on identifying the presence of this AE before symptoms manifest. This allows patients to receive expedited treatment for ILD and subsequently continue to receive T-DXd to treat their cancer, Rodriguez concludes.