Daniel Shao Weng Tan, BSc, MD, PhD

Invited study discussant of the DESTINY-Lung01 trial, Daniel Shao Weng Tan, BSc, MD, PhD, of the National Cancer Center, Singapore, commented: “The trial clearly showed that T-DXd [fam-trastuzumab deruxtecan--nxki] is active in HER2-mutated non–small cell lung cancer (NSCLC). The median progression-free survival and overall survival remain clinically meaningful in this cohort of patients who are refractory to standard therapy. Future studies should focus on optimizing the dose to tackle on-target and off-target resistance and to improve safety, and we need to identify rational combinations,” he said.

One Potential Concern

“The one concern, perhaps, remains the safety profile,” Dr. Tan said. “That will require further evaluation to determine the optimal dosing potential for combinations, so we can improve the durability of response. Until we can properly characterize this and other important aspects, such as central nervous system activity, we need to be cautious about transitioning this therapy to the front-line setting.”

“We also need to give due consideration to strategies to improve HER2 testing rates to expand on the clinical experience, and this really argues for the importance of upfront next-generation sequencing testing in NSCLC,” Dr. Tan stated. 

DISCLOSURE: Dr. Tan reported financial relationships with Novartis, Bayer, Boehringer Ingelheim, AstraZeneca, Lilly, GlaxoSmithKline, C4 Therapeutics, Amgen, Merck, Pfizer, Roche, and Takeda.