Experts on Second-Line Treatment Options for EGFR TKI-Resistant NSCLC

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 second-line treatment options for patients with non–small cell lung cancer (NSCLC) who progressed on first-line EGFR-directed TKIs.

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 executive director of Winship Cancer Institute of Emory University, and a professor and the Roberto C. Goizueta Distinguished Chair for Cancer Research in the 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, Herbst, Ramalingam, Socinski and Wakelee explain that there is a lack of highly effective second-line treatment options beyond chemotherapy in patients resistant to EGFR TKIs. The bispecific-antibody, amivantamab (Rybrevant), is a preferred option, but it is not yet approved beyond patients with EGFR exon-20 insertion mutations. The HER3-targeting antibody-drug conjugate, patritumab deruxtecan (U3-1402), is another promising option for these patients, but it does not strongly correlate with HER3 levels.

The development of targeted therapy may provide a treatment alternative for this patient population. Future research is needed to better identify patients who will benefit from these novel targeted therapies vs traditional non-biomarker driven therapies.