The correlation between the abundance of EGFR T790M mutation and osimertinib response in advanced non-small cell lung cancer

Transl Cancer Res. 2021 Jun;10(6):2895-2905. doi: 10.21037/tcr-21-223.

Abstract

Background: Osimertinib has been adopted as the standard therapy for T790M-mediated acquired resistance to first-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancer (NSCLC). The detection of EGFR T790M can be evaluated using different methods. The association between baseline T790M abundance and osimertinib efficacy has not been fully determined.

Methods: A total of 144 advanced NSCLC patients positive for T790M, at the time of progression, were retrospectively enrolled in this study. The effect of abundance of T790M mutation on the efficacy of osimertinib was explored.

Results: Among the 144 patients receiving T790M testing, 20 (13.9%) had adopted amplification refractory mutation system (ARMS), 63 (43.8%) adopted droplet digital PCR (ddPCR), and 61 (42.4%) used next-generation sequencing (NGS). The objective response rate was 54.2%, the median progression-free survival was 12.0 months, and the overall survival was 23.0 months for the NSCLC patients treated with osimertinib. Three different technologies to assess T790M mutation (including ARMS, ddPCR, and NGS) could accurately predict the efficacy of osimertinib. There was no significant relationship between the abundance of T790M mutation and the efficacy of osimertinib.

Conclusions: ARMS, ddPCR, and NGS are reliable methods to evaluate EGFR T790M mutation. Osimertinib was equally effective for NSCLC patients with various abundance of T790M mutation.

Keywords: Non-small cell lung cancer (NSCLC); T790M abundance; droplet digital PCR (ddPCR); next generation sequencing (NGS); osimertinib.