Abstract

Osimertinib is a third-generation tyrosine kinase inhibitor, initially approved for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) with T790M acquired resistance, and now approved in the first-line setting. However, data supporting the use of osimertinib in untreated brain metastases are limited, although it has established central nervous system (CNS) activity. Our study compares the clinical outcomes of patients experiencing progressing brain metastases treated with cranial irradiation and osimertinib with those treated with osimertinib alone.Forty patients who were treated with osimertinib at the Stanford Cancer Center from November 2015 to December 2016 were identified by searching an electronic medical record database. Eleven patients had progressing brain metastases and did not receive radiation (group A), 9 patients had progressing brain metastases and received radiation when starting osimertinib (group B), and 20 patients had stable brain metastases at the time of initiating osimertinib (group C). Patient and disease characteristics, radiographic responses, and survival outcomes were evaluated retrospectively for the three groups.The CNS response rate was 32.3%. Median time to treatment failure (TTF), overall progression-free survival (PFS), and overall survival (OS) were 10.0 months (95% confidence interval [CI], 4.5-11.8), 8.8 months (95% CI, 6.2-12.1), and 16.2 months, respectively. Median TTF was 15.1 months for group A (95% CI, 1.7-28.5), 7.7 months for group B (95% CI, 0-15.5), and 10.7 months for group C (95% CI, 9.0-12.5). The median PFS was 8.8 months for group A (95% CI, 4.3-13.4), not reached for group B, and 8.4 months for group C (95% CI, 5.6-11.1). The median OS was not reached for group A and C, and was 16.2 months for group B. There was no apparent difference in TTF, PFS, or OS between the three groups.Receiving radiation prior to starting osimertinib for patients with progressing brain metastases did not prolong TTF, PFS, or OS in our series. To minimize the risks of radiation-related toxicity, delaying radiation could be considered for some patients with EGFR-mutant NSCLC with brain metastases who initially respond to osimertinib in the second-line setting.Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor recently approved for the first-line treatment of EGFR-mutant non-small cell lung cancer. Although it appears to have central nervous system (CNS) activity, most clinical trials have excluded patients with untreated, progressing brain metastases. This study included patients with stable and progressing CNS metastases treated with osimertinib and found no apparent differences in median time to treatment failure, time to progression, and overall survival in patients who received osimertinib alone compared with those who received osimertinib and radiosurgery. This may support a clinician's decision to defer radiation for selected patients with untreated brain metastases who are candidates for osimertinib therapy.

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