Dr Levy on the Potential for ADCs in NSCLC

Benjamin Levy, MD, clinical director of Medical Oncology at Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital and associate professor of oncology at Johns Hopkins University School of Medicine in Baltimore, Maryland, discusses antibody-drug conjugates (ADCs) in non–small cell lung cancer (NSCLC) management.

ADCs have emerged as a focal point of clinical interest in NSCLC, Levy explains. Delving into persisting inquiries surrounding the efficacy of ADCs, Levy provides detailed insights into the patient and disease characteristics that may warrant consideration for the use of ADCs and emphasizes the ongoing and prospective research endeavors within the NSCLC treatment domain.

In August 2022, the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of patients with unresectable or metastatic NSCLC harboring activating HER2 mutations after prior systemic therapy. Given the diverse landscape of HER2 alterations, including overexpression, amplification, and mutations, precise molecular profiling is essential to determine patient eligibility, since the indication only covers patients with NSCLC harboring HER2 mutations, Levy says.

Although trastuzumab deruxtecan is currently indicated for use in this patient population after chemotherapy, ongoing investigations could help determine the optimal positioning of the ADC within the treatment continuum, including as a potential first-line option. Additionally, Levy notes that investigating the feasibility of combining ADCs with established modalities such as immunotherapy and platinum-based chemotherapy is warranted to comprehensively delineate safety and efficacy profiles.

Levy notes that the trajectory of ADCs in NSCLC represents an unfolding narrative, with important, new chapters awaiting elucidation. Clinical trials exploring the utility of ADCs across diverse clinical settings, including neoadjuvant and adjuvant contexts, hold promise in revealing their complete therapeutic potential. Particularly, evaluating the synergy between ADCs and immunotherapy stands as a focal point with potential implications for treatment outcomes, Levy concludes.