EGFR T790M testing through repeated liquid biopsy over time: a real-world multicentric retrospective experience

J Thorac Dis. 2022 Sep;14(9):3364-3375. doi: 10.21037/jtd-22-745.


Background: About 15% of non-small cell lung cancers (NSCLCs) harbor epidermal growth factor receptor (EGFR) mutations. Upfront treatment with first and second generation EGFR tyrosine kinase inhibitors (1-2gen TKIs) is superior to chemotherapy. The most frequent resistance mechanism to 1-2gen TKIs is EGFR T790M mutation, which is targeted by osimertinib. T790M mutation can be revealed by liquid biopsy (LB) or by tissue rebiopsy (TB). LB is easily feasible but less sensitive than TB. We focused on repeated LBs and analyzed clinical features associated with EGFR T790M detection.

Methods: This is a retrospective multicenter observational study including EGFR-mutant NSCLC consecutive patients with disease progression (PD) after 1-2gen TKIs and with a first EGFR LB negative for T790M mutation, referred between 2016 and 2019. Aims of the study were to determine the prevalence of T790M mutation using LB in a real-life setting and the prevalence of T790M mutation by repeated LBs. We explored the association of T790M with clinical-pathological features and, through a survey, we evaluated the decision-making process behind LB request. Data on TBs were also collected.

Results: One hundred and ten patients were included in the study, for a total of 326 LBs. Median number of LB per patient was 3.0. The T790M prevalence through LB was 34.5%. Over time, significantly more LBs were requested "at clinical and radiological PD" and "at radiological PD" compared to "arbitrarily". The probability of finding the T790M mutation for a patient across each subsequent LB did not significantly change. Liver and lymph node PD were significantly correlated to T790M positivity. Notably, "at PD" compared to "arbitrarily" LB request and liver, bone or lymph node PD were correlated to the detection of any EGFR mutation in cfDNA. TB was performed in 59.7% of patients with a T790M negative LB and 18.8% of them were T790M positive. In most cases, TB was not feasible due to anatomical reasons. In our study population, the overall T790M prevalence-detected with both LB and TB-was 42.7%.

Conclusions: Repeated LB testing can be useful in a real-life scenario to detect EGFR T790M mutation.

Keywords: EGFR T790M mutation; Non-small cell lung cancer (NSCLC); circulating tumoral DNA; epidermal growth factor receptor tyrosine kinase inhibitors; liquid biopsy (LB).