Experts on the Use of ADCs in HER2-Mutated NSCLC Treatment

Balazs Halmos, MD, Martin F. Dietrich, MD, PhD, Roy S. Herbst, MD, PhD, Suresh S. Ramalingam, MD, FACP, FASCO, Mark Socinski, MD, and Heather Wakelee, MD, FASCO, discuss the use of antibody-drug conjugates (ADCs) in HER2-mutated non–small cell lung cancer (NSCLC).

Balazs Halmos, MD is a professor of Medical Oncology in the Department of Oncology, a professor of Oncology and Hematology in the Department of Medicine, and the chief of Thoracic Oncology at Albert Einstein College of Medicine, Montefiore Medical Center. Martin F. Dietrich, MD, PhD is a medical oncologist at Florida Cancer Specialists & Research Institute.

Roy S. Herbst, MD, PhD, is an ensign professor of medicine in Medical Oncology and professor of Pharmacology, the director of the Center for Thoracic Cancers, and the deputy director of clinical affairs and assistant dean for Translational Research at Yale School of Medicine, and the chief of Medical Oncology and associate cancer center director of Translational Science at Yale Cancer Center, Smilow Cancer Hospital. Suresh S. Ramalingam, MD, FACP, FASCO, is the director of the Lung Cancer Program at Winship Cancer Institute of Emory University, and a professor, assistant dean, Roberto C. Goizueta Distinguished Chair for Cancer Research, and director in the Division of Medical Oncology, Department of Hematology and Medical Oncology at Emory University School of Medicine.

Mark Socinski, MD, is a medical oncologist and executive director of the Thoracic Center at AdventHealth Cancer Institute. Heather Wakelee, MD, FASCO, is professor of medicine and chief of the Division of Oncology at Stanford University School of Medicine, the interim medical director of Stanford Cancer Center, deputy director of Stanford Cancer Institute, and president of the International Association for the Study of Lung Cancer.

Halmos, Dietrich, Herbst, Ramalingam, and Socinski state that there is an increasing interest in the use of ADCs, such as fam-trastuzumab deruxtecan-nxki (Enhertu), which received FDA approval for the treatment of 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 patients with HER2-mutant disease can benefit from ADCs, identifying the correct biomarker can be difficult. Moreover, there are concerns with the prevalence of drug-related interstitial lung disease associated with trastuzumab deruxtecan in patients with HER2-mutated NSCLC. However, safety data suggest that pneumonitis is a manageable adverse effect with a lower dosage of treatment, and the risk of toxicity is not a deterrent relative to the drug's superior efficacy.

Finally, there has been a shift in the treatment paradigm towards the use of ADCs over traditional TKIs. Instead of phasing TKIs out entirely, novel combination regimens that incorporate traditional TKIs could be developed to combat future treatment-resistance.