Dr Tarantino on Updated Safety Data From DESTINY-Breast05 in HER2+ Breast Cancer

“Overall, the striking benefits we’ve seen with T-DXd in DESTINY-Breast05 outweigh the risks, so we should be aware of the risks, ILD in particular, but also realize that this trial led to a major advancement in the field.”

Paolo Tarantino, MD, PhD, a breast medical oncologist and advanced fellow at Dana-Farber Cancer Institute and Harvard Medical School, discussed the clinical implications of a safety update from the phase 3 DESTINY-Breast05 trial (NCT04622319) presented at the 2026 ASCO Annual Meeting, which evaluated post-neoadjuvant fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) vs ado-trastuzumab emtansine (T-DM1; Kadcyla) in patients with high-risk, HER2-positive early breast cancer with residual invasive disease.

Tarantino characterized the updated safety data as reassuring, emphasizing that the investigators effectively distinguished drug-related interstitial lung disease (ILD) from radiation pneumonitis within the trial. Although both entities affect the pulmonary interstitium, they behave differently, he explained. Most cases of T-DXd–related ILD were reversible and manageable with steroid treatment, although some grade 5 events did occur, Tarantino noted. By contrast, radiation pneumonitis cases appeared largely nonreversible, given the predominantly scarring nature of this toxicity, he explained.

Since these two phenomena do not substantially overlap based on the available data, Tarantino stated that the trial findings show that radiation can be safely administered with adjuvant T-DXd or T-DM1. He highlighted 2 additional insights from the presentation. First, patients of Japanese geographic origin were at higher risk of developing ILD, for reasons that remain unclear, warranting heightened awareness, he stated. Second, Tarantino emphasized the rapidly emerging observation that patients with renal impairment also have an elevated risk of developing ILD, representing another population requiring caution.

For these higher-risk patients, Tarantino recommended frequent chest imaging, ideally CT scans every 6 weeks, alongside a clear understanding of the increased ILD risk. Nevertheless, given the striking efficacy benefits observed with T-DXd in DESTINY-Breast05, Tarantino concluded that these clearly outweigh the associated risks.

Supported in part by AstraZeneca and Daiichi Sankyo, content independently developed by OncLive.