The FDA’s oncology advisory ecosystem moved against AstraZeneca’s oral SERD camizestrant in two separate settings, extending uncertainty over the “new paradigm” that would broaden how and when the drug is used. In one case, the FDA advisory committee voted 6–3 that camizestrant did not show a clinically meaningful benefit in a late-stage AstraZeneca study. A second FDA panel action questioned evidence for switching based on Guardant ctDNA ESR1 mutation results: a 6–3 vote said available evidence did not support moving patients to camizestrant based on detected circulating tumor DNA. Together, the outcomes reflect heightened scrutiny on both clinical meaningfulness and the evidentiary threshold for ctDNA-driven treatment switching—key issues for oncology drug developers relying on molecular selection strategies.