376P - The impact of T790M mutation status for later-line osimertinib in non-small cell lung cancer patients with progression on frontline epidermal growth factor receptor tyrosine kinase inhibitor

Background

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which was designed to overcome acquired T790M resistance mutation. This study aimed to evaluate advanced non-small cell lung cancer (NSCLC) patient after first- and second- generation EGFR-TKIs followed by later line osimertinib treatment.

Methods

The clinical data and survival outcomes of advanced NSCLC patients treated with osimertinib followed by frontline line EGFR-TKIs at Chang Gung Memorial Hospitals from 2014 to 2018 were retrospectively reviewed. T790M mutation was detected by tissue sequencing and/or liquid biopsy. Continuous variables were compared using ANOVA test. IBM SPSS Statistics for Windows (Version 23.0, Armonk, NY, USA) was used to perform all statistical analyses.

Results

The patients with NSCLC harboring acquired T790M mutation treated with osimertinib has best objective response rate (52.6%, 25.0%, and 32.0%, p=0.044), disease control rate (79.3%, 41.7%, and 68.0%, p=0.011) and progression-free survival (PFS, medium PFS, 12.6, 3.1, 10.4 months, p=0.001) among three groups (positive, negative and unknown T790M). However, the difference was significantly found between positive and negative T790M but not positive and unknown T790M. Univariate analysis was performed to identify potential prognostic factors for PFS of osimertinib in 172 patients treated with osimertinib. Lung metastasis (p<0.001), brain meta (p<0.009), number of metastatic sites(p<0.001), PFS of frontline EGFR-TKIs (p=0.03) and T790M status (p=0.006) were identified as prognostic factors for PFS of osimertinib. Multivariate analysis showed lung metastasis (p<0.001), PFS of frontline EGFR-TKIs, T790M status were still independent prognostic factors.

Conclusions

This study confirmed that the greater efficacy of later-line osimertinib for NSCLC with T790M mutation than without T790M mutation. Detection of T790M mutation after front-line treatment (first- and second-generation EGFR-TKI) is crucial to prolong the survival in NSCLC patients harboring EGFR mutation.

Clinical trial identification

This study was approved by the Institutional Review Board (IRB) of CGMH (IRB No.:201901395B0C501). Patient consent to participate was not required due to the retrospective nature of this study.

Editorial acknowledgement

Legal entity responsible for the study

Chang Gung Memorial Hospital at Linkou.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.