Invited discussant Patricia LoRusso, DO, PhD, of Yale School of Medicine, said to the assembled audience at the 2022 ASCO Annual Meeting: “I see you are as excited about these data as I am,” after the applause ended following Dr. Modi’s presentation. “I want to thank our colleagues for helping to change the face of HER2-low breast cancer,” she added.

“Overall survival is the most important endpoint in clinical trials. There was a survival advantage in hormone receptor–positive and hormone receptor–negative patients and an overall survival advantage for T-DXd [fam-trastuzumab deruxtecan-nxki] over physician’s choice of therapy,” she emphasized.

Patricia LoRusso, DO, Ph

Quantifiable Assay Needed

Now that it is known that patients with HER2-low disease may benefit from this therapy, an accurate test for levels of HER2 expression becomes increasingly important. Dr. LoRusso noted that the immunohistochemistry (IHC) test currently used in the United States has some problems. “In one paper, there is a substantial discordance between readouts of IHC 0, IHC 1+, IHC 2+. This is disconcerting, as now we have a drug for HER2-low disease,” she stated. 

Dr. LoRusso said that a new quantifiable assay would have some advantages over IHC “to determine true tumor positivity for HER2, to overcome subjectivity of the human eye, and to be reproducible and tumor-agnostic…. Many institutions are now using [fluorescence in situ hybridization] instead of IHC. Imagine the number of patients who will be deprived of this exciting agent without a quantifiable assay,” she said.

“What is our destiny?” she asked rhetorically. “Should we change our standard of care based on this study? My answer is yes, absolutely.” 

DISCLOSURE: Dr. LoRusso has received honoraria from Five Prime Therapeutics; has served as a consultant or advisor to AbbVie, ABL Bio, Agenus, Agios, Astellas Pharma, AstraZeneca, BAKX Therapeutics, Bayer, Black Diamond Therapeutics, Compass Therapeutics, Cybrexa Therapeutics, CytomX Therapeutics, EMD Serono, Five Prime Therapeutics, Genentech, Genmab, GlaxoSmithKline, Halozyme, I-Mab, ImCheck Therapeutics; ImmunoMet Therapeutics, IQvia, Kineta, Kyowa Kirin International, MacroGenics, Mekanistic Therapeutics, Molecular Templates; Pfizer; QED Therapeutics; Relay Therapeutics; Roche/Genentech, Salarius Pharmaceuticals, Seattle Genetics, Shattuck Labs, Silverback Therapeutics, SK Life Sciences, Sotio, ST Cube, Stemline Therapeutics, Takeda, Trial to Reduce IDDM in the Genetically at Risk (TRIGR), TYME, and Zentalis Pharmaceuticals; and has received institutional research funding and reimbursement for travel, accommodations, and other expenses from Genentech.