71yo female diagnosed with adenocarcinoma right middle lobe lung. Stage: clinical T2aN3M1, with solitary brain metastasis. EGFR exon 19 (+), TMB low. Completed chemoRT with Taxol/Carboplatin, but with sequelae of renal impairment. Subsequently started osimertinib 80mg with resolution of brain metastasis and stable right hilar mass. Surveillance scans 4 to 5 months later showed new, solitary brain metastasis, but no other sites of disease. Osimertinib increase to 160mg. Brain imaging began 2 months later and was stable. But MRI 1 month later showed progression with bilateral cerebrum and cerebellar deposits, as well at left sphenoid sinus and extension to ipsilateral orbit with mild exophthalmos. There is also suggestion of leptomeningeal disease. Imaging of the remaining neuro-axis, lumbar puncture for cytology and referral to radiation oncology are in process. Question: 1) Are there any other investigative studies that need to be undertaken? 2) What would you recommend for next line of therapy? I'm tentatively planning for a retrial of carboplatin, but with pemetrexed, though hesitant about adding immunotherapy, given increased risk for immune-mediated toxicity following TKI. I would be interested on your advice in her care and prognosis.

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