What systemic therapy would you offer to a patient with metastatic EGFR exon 19 deleted NSCLC to the brain with isolated CNS progression while on osimertinib 80 mg and progressed through WBRT?

If this is isolated CNS progression, the answer will depend on the number of metastatic sites. This is worth a conversation with your radiation oncologist. If there are 1-5 sites progressing within the CNS, it may be reasonable to consider treating these with SRS (even if patients have had prior whole brain radiotherapy) using an oligoprogression paradigm and staying on osimertinib. If the CNS progression is more widespread, then you can attempt a dose escalation to 160 mg PO daily. A retrospective multi-institutional series [Piper-Vallillo et al., PMID 35637759] found 3-6 month improvement in CNS control with dose escalation to osimertinib 160 mg PO daily, but I would get a short interval MRI to confirm that this strategy is working. If th...