Clinical features and progression pattern of acquired T790M positive compared with T790M negative EGFR mutant Non-Small Cell Lung Cancer: catching tumor and clinical heterogeneity over time through liquid biopsy

Abstract Background Clinical-pathological predictors of acquired T790M Epidermal Growth Factor Receptor (EGFR) mutation in Non-Small Cell Lung Cancer (NSCLC) Caucasian patients progressing after first-/second-generation tyrosine kinase inhibitors (TKIs) is an open field for research. On the same way, the best time point for T790M detection by liquid or tissue biopsy after disease progression is currently matter of debate. Patients and Methods This is an observational study at 7 Italian Centers enrolling EGFR-mutant NSCLC patients progressing after first-/second-generation EGFR TKIs, between 2014 and 2018, aiming at comparing baseline clinical-pathological features and progression patterns in acquired T790M positive compared with T790M negative cases. Results 235 patients received first-line treatment with gefitinib (N=126, 53%), erlotinib (N=51, 22%) or afatinib (N=58, 25%). In 120 (51%) cases T790M was detected in liquid, tissue biopsy or both. Age younger than 65 years (p=0.037), the presence of common mutations (p=0.004) and better response to first-line TKI (p=0.023), were correlated with T790M positivity. T790M detection was associated with higher number of new progressing sites (p=0.04), liver progression (p=0.002) and a lower frequency of lung metastases (p=0.027). When serial liquid biopsies were performed (N=15), an oligoprogressive disease was correlated with a negative test outcome, while systemic progression was observed at the time of T790M positivity. Conclusion This study on a Caucasian population showed that age, type of EGFR mutation at diagnosis, response to first-line treatment and peculiar progression pattern are associated with T790M status. Serial liquid biopsy might be useful for treatment selection, especially when tissue rebiopsy is not feasible.