Dr Vivekanandarajah on Identifying HER2-Mutated NSCLC in the Community Setting

Abhirami Vivekanandarajah, MD, hematologist-oncologist, New York Cancer & Blood Specialists, discusses how she tests for and identifies patients with HER2-mutated non–small cell lung cancer (NSCLC) in the community setting, as well as the role of TKIs and antibody-drug conjugates (ADCs) in the first- and second-line treatment for HER2-mutated NSCLC.

Vivekanandarajah states that her approach to the management of metastatic NSCLC in community practice typicallyinvolves conducting tissue-based genetic testing. She utilizes KRAS-specific follicular testing for tissue biopsies and simultaneously sends samples for liquid biopsy testing. Liquid biopsies often yield faster results compared with tissue-based testing, allowing for more timely identification of actionable mutations, Vivekanandarajah explains. Comprehensive genomic profiling using next-generation sequencing (NGS) is important for all relevant alterations, including HER2 mutations, which are increasingly being recognized as critical targets in NSCLC, Vivekanandarajah emphasizes.

FDA approval for ADCs targeting HER2 mutations is limited to the second-line setting in NSCLC, she notes. In August 2022, the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu) for adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 mutations, as detected by an FDA-approved test, and who have received previous systemic therapy. Although no data currently support use of ADCs in the first-line setting, clinical trials are ongoing to assess the efficacy of these agents as an initial treatment option. These trials are particularly focused on this rare subset of patients and aim to establish the potential benefits of utilizing targeted therapies earlier in the treatment sequence, Vivekanandarajah states.

When a specific target such as HER2 is identified, it is most effective to employ the corresponding targeted therapy up-front, Vivekanandarajah asserts. Starting with chemotherapy and reserving HER2-targeted therapies for later lines of treatment may not always be ideal, as patients may sometimes deteriorate to a point where they are no longer fit to receive these potentially beneficial drugs, Vivekanandarajah explains. Initiating targeted treatments earlier may improve outcomes by maximizing the therapeutic benefit when patients are in a better overall condition, she concludes.