Pragmatic Management of EGFR-Mutant NSCLC After Progression on Osimertinib: Canadian Expert Perspectives

The management of epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after progression on osimertinib is becoming increasingly complex, particularly in Canada, where access to diagnostic testing and newer therapies remains uneven. Although treatment is evolving with regimens such as amivantamab-lazertinib (MARIPOSA/MARIPOSA-2) and osimertinib plus chemotherapy (FLAURA2), access to such treatments in first and second lines varies across provinces. This article provides a pragmatic Canadian perspective on post-osimertinib management informed by expert roundtable discussions, a focused clinician survey, and the contemporary literature. Key challenges identified include delays and barriers related to tissue biopsy, next-generation sequencing, timely immunohistochemistry in time to influence treatment decisions and access to novel therapies. These gaps reduce the ability to individualize care and often force clinicians to rely on platinum-pemetrexed therapy as the default systemic backbone, even when biologically relevant resistance mechanisms exist, highlighting that post-osimertinib care in Canada remains shaped as much by access and system constraints as by emerging evidence.