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Top Line: What is the intracranial response rate of osimertinib in patients with EGFR 790M mutated NSCLC brain metastases that have never received radiation?

The Study: Evaluating true intracranial activity of emerging targeted agents is challenging as many patients with measurable intracranial disease have a mix of lesions previously treated or untreated with radiation. The OCEAN study was designed to prospectively evaluate the intracranial activity of the EGFR-TKI osimertinib in patients with radiation-naive brain metastases. Patients had to have EGFR T790M mutated non-small cell lung cancer that progressed on a prior first or second-line EGFR-TKI, and brain metastases had to be at least 5 mm in size. The median brain metastasis size was 8.4 mm with a range of 5 to 27 mm.  They received osimertinib 80 mg daily. MRI was performed every 6 weeks for the first year and every 3 months thereafter. Among 39 patients evaluated by PAREXEL criteria, the brain metastasis response rate (BMRR) was 66.7% with 10% having a complete response and 56% having a partial response. Among 20 patients evaluated by RECIST criteria, the BMRR was 70% with 5% having a CR and 65% having a PR. Median brain metastasis progression-free survival was 25.2 months. An important finding of the study was that blood concentration of osimertinib was not associated with BMRR. A second arm of the OCEAN study is evaluating intracranial activity when osimertinib is the first-line treatment as opposed to after EGFR-TKI progression. It’s no argument that osimertinib is active in the CNS. The question is whether this will be added to the well-established efficacy of local therapy to further improve intracranial control or whether the results are “good enough” to go it alone.

TBL: Two thirds of patients with radiation-naive brain metastases from EGFR mutated NSCLC have at least a partial response to osimertinib. | Yamaguchi, J Thorac Oncol 2021