Dr. Levy on Overcoming Osimertinib Resistance in EGFR-Mutant NSCLC

Benjamin P. Levy, MD, clinical director, Medical Oncology, associate professor of oncology, Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, discusses potential strategies to overcome resistance to osimertinib (Tagrisso) in EGFR-mutant non–small cell lung cancer (NSCLC). 

Patients whose tumors harbor EGFR mutations often develop resistance to osimertinib. However, clinical guidelines as to what treatment is optimal for these patients are inconclusive, Levy explains. Data emerged during the 2021 ASCO Annual Meeting showing that the combination of lazertinib (YH25448) and amivantamab-vmjw (Rybrevant) elicited clinically meaningful activity in patients with chemotherapy-naïve, EGFR-mutant NSCLC who had progressed on osimertinib. The regimen has been utilized in other tumor types but offers a potential novel addition to the lung cancer armamentarium. 

Additionally, patritumab deruxtecan (U3-1402), a HER3-directed antibody-drug conjugate (ADCs), demonstrated a confirmed objective response rate of 39% in patients with EGFR-mutant NSCLC who were resistant to EGFR TKIs, Levy says. 

Moreover, the field of lung cancer treatment has evolved beyond using small molecule inhibitors to target novel targets, Levy explains. Oral therapies, bispecific antibodies, and ADCs are being developed for use in offering meaningful outcomes for patients with lung cancer, Levy concludes.