New data confirm a risk for interstitial lung disease (ILD) in women with HER2-positive metastatic breast cancer receiving the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) but show that most cases are mild and occur early. One "important takeaway is that our experience shows us that if detected early and managed quickly and appropriately, that this is a manageable side effect. And that when it does occur, it typically occurs within the first year of treatment, which is important information for us to know," Dr. Charles Powell, director of the Mount Sinai-National Jewish Health Respiratory Institute in New York, told Reuters Health by phone. At the ESMO Breast Cancer Virtual Congress, Dr. Powell reported an analysis of 245 women with heavily pretreated HER2-positive metastatic breast cancer who received T-DXd for a median 9.7 months as part of three clinical trials. During treatment, 38 (15.5%) women experienced an ILD event that was adjudicated as related to T-DXd therapy. Most ILD events were mild (grade 1 or 2, 12.2%). One patient each had grade-3 and grade-4 events (0.4%) and six had a grade-5 ILD event (2.4%). The majority of cases of ILD occurred within the first 12 months of therapy (median time to first ILD event, 5.6 months) and the risk of any-grade ILD event decreased thereafter (conditional probability, 1.8%), which suggests that toxicity is not cumulative. "We know that a significant number of patients with metastatic breast carcinoma who have been heavily pretreated with multiple different chemotherapy regimens and still experience disease progression have a response to treatment with this antibody-drug conjugate with extended progression-free survival time," Dr. Powell told Reuters Health. "And we know that that benefit is accompanied by a risk, such as is the case for all treatments and for all diseases, especially in oncological drugs. And amongst the risks is that of interstitial lung disease, which was identified early on as a potentially clinically significant risk for patients treated with this compound," he added. "What we're adding here is data from the accumulating experience through clinical trials of this compound in patients with breast cancer. And in this report, we're focusing on patients with breast cancer in single-arm studies, who were treated with the dose of 5.4 milligrams per kilogram of trastuzumab deruxtecan," he said. Going forward, it will be important identify which patients are most at risk for ILD with trastuzumab deruxtecan therapy, Dr. Powell said. Funding for the study was provided by AstraZeneca. In 2019, the company entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan. Dr. Powell has financial relationships with both companies. —Megan Brooks Source
