Would you offer upfront osimertinib rather than whole brain irradiation for a patient with stage IV, EGFR exon 19 mutated lung adenocarcinoma who presents with leptomeningeal metastases?

As always a challenging situation is raised by a question in this forum. Clearly more clinical information is relevant. Not clear as to what "The patient 'presented' with leptomeningeal metastases" means. 

In many patients, asymptomatic leptomeningeal metastases are detected on MRI scans of the brain. So it is not clear from the question if the patient had symptoms at presentation or the findings of leptomeningeal metastases were detected on routine scans. In many clinical trials, presence of leptomeningeal metastases was an exclusion criteria. I am not certain if leptomeningeal metastases was an exclusion criteria in the Osimertinib phase III trials. 

However Osimertinib was evaluated in patients with leptomeningeal metastases in a small phase I/II study, BLOOM study. All these patients were previously treated with EGFR-TKIs and were not treatment naive. Thirty two patients were treated at a dose of 160 mg. Durable clinical benefit was observed in this patient population. There is no randomized data available comparing Osimertinib with whole brain RT versus Osimertinib alone. 

In this particular patient if the patient had asymptomatic leptomeningeal metastases, I would consider doing spinal MRI to ascertain the extent of leptomeningeal metastases and start this patient on osimertinib without whole brain RT. I would seek approval for the 160 mg dose. 

If the patient had symptoms then I would consult our Neuro-oncology team. I would lean towards starting such a patient on Osimertinib so as to address both leptomeningeal metastases and systemic metastases with a single therapy but would finalize therapy after seeking input from our Neuro-Oncology team.