*November 2020*

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, efficiently penetrates the blood-brain barrier. This study explored whether treatment with osimertinib leads to improved overall survival (OS) for patients with EGFR-mutated NSCLC with leptomeningeal metastases (LM) compared with those not treated with osimertinib.

For the 351 patients with LM included in the analysis, the median OS (mOS) was 8.1 months (95% confidence interval [CI]: 7.2–9.0). T790M mutation was detected in 88 of 197 patients tested, and a total of 110 patients were treated with osimertinib after LM. No difference in mOS according to T790M mutational status (10.1 mo [95% CI: 4.31–15.82] versus 9.0 [95% CI: 6.81–11.21], p = 0.936) was found. Nevertheless, patients treated with osimertinib had a superior OS of 17.0 months (95% CI: 15.13–18.94) compared with those not treated with osimertinib who had a mOS of 5.5 months (95% CI: 4.34–6.63), regardless of T790M mutational status (hazard ratio: 0.36 [95% CI: 0.28–0.47], p < 0.001). This was also considerably longer even than the mOS of 8.7 months (95% CI: 7.01–10.39) of those who were never treated with osimertinib but had first- or second-generation EGFR tyrosine kinase inhibitors.

Conclusions

Osimertinib is a promising treatment option for EGFR-mutated NSCLC with LM regardless of T790M mutational status. Read more.

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