Interstitial lung disease
After a median treatment duration of 10 months, all but one patient had at least one drug-related adverse event. Grade 3 or greater drug-related adverse events occurred in 48.4% of patients, and serious drug-related events occurred in 12.5%.
A total of 25 patients had ILD of any grade, including 5 with grade 1, 15 with grade 2, 1 with grade 4, and the aforementioned 4 patients who died from the disease.
In the four patients with fatal ILD, onset ranged from 63-146, with the deaths occurring 9-60 days after ILD diagnosis. Three of the patients had received steroids as part of their ILD treatment.
The investigators recommend close monitoring of patients for signs and symptoms of lung disease, including fever, cough, or dyspnea. They also recommend that patients with suspected ILD be evaluated with high-resolution CT and testing for pulmonary function and oxygen saturation, ideally under consultation with a pulmonologist.
However, despite the known cardiotoxic effects of trastuzumab, there were no reported cases of heart failure with decline in left ventricular ejection fraction, and only three patients had a decrease in left ventricular ejection fraction, none of which grade 4.
“The response rate and overall efficacy observed with trastuzumab deruxtecan in this study appear to substantially exceed those of currently available HER2-directed regimens and new agents in development, although cross-trial comparisons must be interpreted with caution,” the investigators wrote in the New England Journal of Medicine.
The study was funded by Daiichi Sankyo and AstraZeneca. Dr. Krop disclosed consulting fees, honoraria from each company, and research support from Genentech/Roche and Pfizer.
SOURCE: Krop I et al. SABCS 2019, Abstract GS1-03.