Invited discussant of TROPION-Lung01, Sarat Chandarlapaty, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York, was cautiously optimistic about this new treatment option.

Sarat Chandarlapaty, MD, PhD

“Dato-DXd [datopotamab deruxtecan] has a benefit over standard-of-care docetaxel in the second-line setting. There was a modest improvement in the total population, but a clear benefit was observed in the nonsquamous group. It may be that specific groups derive the benefit of this antibody-drug conjugate, but it is not clear why. Given the improvement in the nonsquamous group and the reduced toxicity, I would consider prescribing Dato-DXd in this setting,” Dr. Chandarlapaty said.

“However, the elephant in the room is whether the greater promise of antibody-drug conjugates is being delivered upon. In the case of fam-trastuzumab deruxtecan-nxki, we found a sweet spot in HER2-positive breast cancer. An avalanche of different antibody-drug conjugates is coming, and it is unclear how best we will use them: in unselected patients, or will we figure out which ones for which patients? We need to identify the rapid progressors and the patients who do really well. We need translational studies to determine how resistance develops after benefit. And we need to explore relevant biomarkers if we want to achieve a durable benefit,” he concluded. 

DISCLOSURE: Dr. Chandarlapaty has served as an advisor to AstraZeneca, Boxer Capital, Nuvalent, SAGA Diagnostics, NeoGenomics Laboratories, Eli Lilly, Effector Tx, Genesis Tx, Prelude Tx, Casdin Capital, Blueprint, and Novartis; has financial relationships with Totus Med, Odyssey Bio, and Effector Tx; and has received research grants from Daiichi Sankyo and AstraZeneca.