In the phase 3 trial DESTINY-Breast05, 1635 women with residual disease following neoadjuvant systemic therapy for HER2+ breast cancer were randomized to post-op trastuzumab deruxtecan (T-DXd) versus standard trastuzumab emtansine (T-DM1). The real headline here is this manuscript includes a radiotherapy detail: “Among patients who received radiotherapy, trial therapy could be initiated concurrently with radiotherapy or after completion of radiotherapy (sequential).” Another important finding: T-DXd halved invasive disease-free survival at three years (92.4% vs. 83.7%), with fewer distant and intracranial recurrences across subgroups. Toxicities differed by agent, with notably more interstitial lung disease (9.6%, including two fatal cases) following T-DXd, underscoring the need for vigilant continued monitoring of how T-DXd may interact with prior radiation dose to lung among women for whom this is now arguably the new post-op standard. For now, ILD does not appear to occur more frequently when radiation is in this mix, either concurrent or sequential to T-DXd. | Loibl, N Engl J Med 2025
