Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Clinical features and progression pattern of T790M+ compared with T790M-EGFR mutant NSCLC.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20612)
Author(s): Giulia Pasello, Alessandro Dal Maso, Martina Lorenzi, Elisa Roca, Sara Pilotto, Marianna Macerelli, Valentina Polo, Alessandro Del Conte, Giorgia Nardo, Vanessa Buoro, Daniela Scattolin, Sara Monteverdi, Loredana Urso, Elisabetta Zulato, Stefano Frega, Laura Bonanno, Stefano Indraccolo, Fiorella Calabrese, Pierfranco Conte; Istituto Oncologico Veneto IOV IRCCS, Padova, Italy; Istituto Oncologico Veneto IRCCS, Padova, Italy; Oncology Department, Spedali Civili Hospital, Brescia, Italy; University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy; Department of Oncology, University Hospital of Udine, Udine, Italy; Azienda ULSS 2 Marca Trevigiana, Treviso, Italy; Oncology Unit Pordenone CRO Aviano, Aviano, Italy; Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IRCCS, Padova, Italy; Department of Medicine (DAME) - University of Udine, Udine, Italy, Udine, Italy; University of Padova, Padova, Italy; University of Verona, Verona, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy; Medical Oncology 2, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; Department of CardioThoracic and Vascular Sciences, University of Padova, Padova, Italy; University of Padova and Istituto Oncologico Veneto, Padova, Italy
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.