Clinical read The class that was built to rescue patients who had run out of options is now being recommended as the first thing they receive, and two opinions in one week is the moment that becomes undeniable. The commercial logic is stark: in metastatic breast cancer more than half of patients never reach a second line, so a therapy confined to later lines reaches a fraction of the people who have the disease. Moving to first line expands the treated population and lengthens time on drug at the same time. Two things deserve more attention than they will get. The first is the gap between the two results, 13.8 months of additional progression-free survival for Enhertu against 3.4 for Trodelvy, which are not comparable diseases but are being greeted with the same language, and in both cases overall survival has not matured. The second is exposure. Enhertu carried interstitial lung disease in 12.1 percent of patients in DESTINY-Breast09, including two fatal events. A toxicity profile that is acceptable when a patient has exhausted alternatives is a different calculation when the same drug is given first, for longer, to patients who have other options. Note also what these approvals do to the older biologics: the ADC becomes the backbone and trastuzumab-era pertuzumab and Keytruda become the partners riding alongside it, which reverses the relationship those franchises were built on and gives each a new first-line indication at a convenient moment.