The COPERNICUS study, an ongoing phase two trial, evaluated amivantamab-based regimens in EGFR-mutant non-small cell lung cancer across two cohorts, first-line and post-osimertinib progression, with a key focus on implementing mandatory prophylactic skin and DVT regimens, resulting in dramatically lower rash rates (4% grade 3+) compared to the original MARIPOSA trial. Discussion centered on the patient burden of chronic prophylaxis medications, with panelists noting that the supportive care requirements are comparable to those of chemotherapy-based regimens, and that subcutaneous administration reduces clinic time as a meaningful trade-off. A substantive debate emerged around whether all EGFR-mutant patients require treatment intensification, with panelists calling for better biomarker refinement, including ctDNA clearance, TP53 status, and EGFR overexpression, to identify candidates who may not benefit from escalated therapy. CNS progression management was also debated, with data from ASCO 2026 suggesting no survival difference between upfront and delayed brain radiation, though panelists emphasized the value of regimens with strong intracranial activity in preventing difficult-to-salvage CNS progression.
