Osimertinib improves overall survival in EGFR-mutated non-small cell lung cancer patients with leptomeningeal metastases regardless of T790M mutational status

Lung Cancer
12/07/2020

Lee J, et al. J Thorac Oncol 2020.

ABSTRACT

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

METHODS: From October 2008 to October 2019, patients with EGFR-mutated NSCLC and cytologically confirmed LM were retrospectively analyzed for OS according to osimertinib treatment and T790M mutational status. OS was defined as the time from diagnosis of LM to death.

RESULTS: For the 351 LM patients included in 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 significant difference in mOS was demonstrated according to T790M mutational status (10.1 months [95% CI 4.31-15.82] vs. 9.0 [6.81-11.21], P= 0.936). However, patients treated with osimertinib showed a superior OS of 17.0 months (95% CI, 15.13-18.94) compared with those not treated with osimertinib who showed a mOS 5.5 months (95% CI 4.34-6.63) regardless of T790M mutational status (HR 0.36; 95% CI 0.28-0.47, P <0.001). This was considerably longer even compared to those who were never treated with osimertinib but with first-/second-generation EGFR TKIs showing a mOS of 8.7 months (95% CI 7.01-10.39).

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