Steven J. Isakoff, MD, PhD

Steven J. Isakoff, MD, PhD, a medical oncologist at Massachusetts General Hospital, Boston, commented on the results of the DESTINY-Breast01 trial. “These data are extraordinarily encouraging, suggesting we will have another new option for patients with metastatic HER2-positive breast cancer. The response rate and clinical benefit rate are very impressive in this heavily pretreated population, especially after treatment with ado-trastuzumab emtansine (T-DM1). However, this is a single-arm study, and although it may lead to accelerated approval, we still need to see the results of the ongoing phase III DESTINY trials. Full approval will likely be contingent on the phase III results.”

Questions Remain

“The landscape for treating HER2 disease continues to get more crowded, which gives us more options, but the best sequencing strategy needs to be defined,” Dr. Isakoff stated. He also noted that the toxicity with [fam-] trastuzumab deruxtecan (T-DXd) seems to be more substantial than with T-DM1 and that interstitial lung disease is a concern.

“Clearly, early recognition of interstitial lung disease and aggressive management will be important when using this drug. It remains to be seen how this drug compares with T-DM1 head to head,” posed Dr. Isakoff.

“The response rate of 60.9% is incredible. The waterfall plot shows some shrinkage or stable disease in all but four patients. It’s unheard of to see such an impressive waterfall plot in this setting,” Dr. Isakoff said. 

DISCLOSURE: The study was supported by Daiichi Sankyo and AstraZeneca. Dr. Isakoff has served as a consultant or advisor to AbbVie, Genentech/Roche, Hengrui Therapeutics, Immunomedics, Myriad Genetics, and Puma Biotechnology; and has received institutional research funding from AbbVie, AstraZeneca/MedImmune, Genentech, Merck, OncoPep, and PharmaMar.