Clinical features and progression pattern of T790M+ compared with T790M-EGFR mutant NSCLC.

Abstract

e20612 Background: Acquired T790M EGFR mutation (mut) is not predictable by any clinical-pathological feature. The best time point for T790M mut detection by liquid or tissue biopsy is currently undefined. Methods: This is an observational study at 6 Italian Centers enrolling EGFR mutant NSCLC patients (pts) progressing after first/second generation EGFR TKI, between 2014 and 2018. The primary endpoint of the study was to compare clinical features in acquired T790M+ compared with T790M- cases. The secondary endpoint was to assess different progression (PD) patterns between the two groups. We also explored the PD pattern at the time of cfDNA negativity and subsequent positivity, in a subgroup of pts receiving serial liquid biopsies. Statistical analysis was performed by the Chi-square test to correlate clinical features with T790M status, and by the Kaplan-Meier estimator to evaluate median progression free (mPFS) and overall survival (mOS). Multiple logistic regression and log-rank tests were applied. Results: 219 pts were included. Median follow-up since diagnosis was 25 months. First line treatment was gefitinib (N = 119, 54%), erlotinib (N = 48, 22%) or afatinib (N = 52, 24%). In 108 (49%) cases a T790M acquired mut was detected in liquid (70), tissue (31) biopsy or both (7). Age younger than 65 years ( p= 0.05) and presence of sensitizing exon 19 deletion ( p= 0.04) were correlated with T790M mut; this association was confirmed at multivariate analysis ( p= 0.010 and p= 0.006, respectively). At the time of PD, new PD sites ( p= 0.005) and liver PD ( p< 0.001) were more commonly observed in T790M+ group; at multivariate analysis statistical significance was confirmed ( p= 0.01 and p= 0.008, respectively). Longer mOS was observed in T790M+ cases at univariate (53 versus 22 months, p < 0.0001) and multivariate analysis. In 13 pts undergoing serial liquid biopsies, an oligoprogressive disease was correlated with a negative test outcome, while PS/symptoms worsening, higher number of new lesions and PD sites were observed at the time of T790M positivity, although without statistical significance. Conclusions: This is the first caucasian series showing different clinical features and progression patterns of T790M+ versus T790M- EGFR mutant NSCLC.