The Status of the EGFR T790M Mutation is associated with the Clinical Benefits of Osimertinib Treatment in Non-small Cell Lung Cancer Patients: A Meta-Analysis

J Cancer. 2020 Mar 4;11(11):3106-3113. doi: 10.7150/jca.38411. eCollection 2020.

Abstract

Background and Purpose: Pervious studies have demonstrated that the loss of EGFR T790M after Osimertinib treatment may be the cause of Osimertinib resistance. Here, we conducted a meta-analysis to evaluate the association between the persistence of EGFR T790M and the clinical benefits of Osimertinib in non-small cell lung cancer (NSCLC) patients with baseline EGFR T790M mutation. Experimental design and Methods: PUBMED, EMBASE, and Cochrane databases were searched for eligible studies that provided the survival outcomes including overall survival (OS), progression-free survival (PFS) or time to discontinuation (TTD) data for each patient treated with Osimertinib with the status of the T790M mutation tested after Osimertinib resistance. The hazard ratios (HRs) and their 95% confidence intervals (CI) were calculated for each study. Results: In total, eight eligible studies were included in the analysis, among which six studies provided the data on PFS, and the other two studies provided the TTD data. Overall, 312 patients (151 patients with the persistence of T790M) were identified. The persistence of T790M was associated with longer PFS (HR, 0.40; 95% CI, 0.19-0.84; P=0.01) and TTD (HR, 0.54; 95% CI, 0.39-0.76; P=0.0004). Furthermore, overall analysis the survival outcomes including PFS and TTD subgroups also showed preferable clinical benefits for patients with the T790M persistence (HR, 0.57; 95%CI, 0.45-0.73; P<0.00001). Conclusions: Our findings confirm the persistence of T790M is associated with the clinical benefits of Osimertinib in NSCLC patients with baseline EGFR T790M mutation treated with Osimertinib.

Keywords: EGFR T790M mutation; Osimertinib; meta-analysis; non-small cell lung cancer; resistance.