An FDA oncology advisory committee voted 6–3 that evidence does not support switching patients to AstraZeneca’s camizestrant based on ESR1 mutations detected in circulating tumor DNA. The panel’s discussion centered on whether the proposed ctDNA-based strategy has enough clinical support to change the treatment paradigm. The decision adds another regulatory headwind for ctDNA-guided treatment selection in HR+/HER2− metastatic breast cancer, where ESR1 alterations are common. It also highlights the committee’s skepticism about moving earlier in-line decisions without stronger outcome data tied to the diagnostic approach. For developers of companion diagnostics and SERD-related strategies, the panel’s vote underscores the evidentiary bar for linking assay results to clinically meaningful endpoint improvements.