Alessandro Dal Maso1, Martina Lorenzi1, Elisa Roca2, Sara Pilotto3, Marianna Macerelli4, Valentina Polo5, Fabiana Letizia Cecere6, Alessandro Del Conte7, Giorgia Nardo8, Vanessa Buoro4, Daniela Scattolin9, Sara Monteverdi3, Loredana Urso9, Elisabetta Zulato8, Stefano Frega10, Laura Bonanno10, Stefano Indraccolo8, Fiorella Calabrese11, PierFranco Conte1, Giulia Pasello12. 1. Department of Oncology 2, Istituto Oncologico Veneto - IRCCS, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. 2. Department of Medical Oncology, ASST - Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy. 3. Department of Medical Oncology, University of Verona, AOUI Verona, Verona, Italy. 4. Department of Medical Oncology - ASUIUD Santa Maria della Misericordia, Udine, Italy. 5. Oncology Unit, AULSS 2 Marca Trevigiana, Ca' Foncello Hospital, Treviso, Italy. 6. Department of Oncology 1, Regina Elena National Cancer Institute IRCCS Rome, Rome, Italy. 7. Department of Medical Oncology and Immunorelated Tumors, Centro di Riferimento Oncologico (CRO) - IRCCS, Aviano (PN), Italy. 8. Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto - IRCCS, Padova, Italy. 9. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. 10. Department of Oncology 2, Istituto Oncologico Veneto - IRCCS, Padova, Italy. 11. Pathology Unit, Department of Cardio-Thoracic and Vascular Sciences, University of Padova, Padova, Italy. 12. Department of Oncology 2, Istituto Oncologico Veneto - IRCCS, Padova, Italy. Electronic address: giulia.pasello@iov.veneto.it.
Abstract
BACKGROUND: Clinical-pathologic predictors of acquired T790M epidermal growth factor receptor (EGFR) mutation in Caucasian patients with non-small-cell lung cancer (NSCLC) progressing after first-/second-generation tyrosine kinase inhibitors (TKIs) is an open field for research. Similarly, 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 patients with EGFR-mutant NSCLC progressing after first-/second-generation EGFR TKIs, between 2014 and 2018, aiming at comparing baseline clinical-pathologic features and progression patterns in acquired T790M-positive compared with T790M-negative cases. RESULTS: A total of 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 biopsy, tissue biopsy, or both. Age younger than 65 years (P = .037), the presence of common mutations (P = .004), and better response to first-line TKI (P = .023) were correlated with T790M positivity. T790M detection was associated with higher number of new progressing sites (P = .04), liver progression (P = .002), and a lower frequency of lung metastases (P = .027). When serial liquid biopsies were performed (N = 15), an oligoprogressive disease was correlated with a negative test outcome, whereas 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.
BACKGROUND: Clinical-pathologic predictors of acquired T790Mepidermal growth factor receptor (EGFR) mutation in Caucasian patients with non-small-cell lung cancer (NSCLC) progressing after first-/second-generation tyrosine kinase inhibitors (TKIs) is an open field for research. Similarly, 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 patients with EGFR-mutant NSCLC progressing after first-/second-generation EGFR TKIs, between 2014 and 2018, aiming at comparing baseline clinical-pathologic features and progression patterns in acquired T790M-positive compared with T790M-negative cases. RESULTS: A total of 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 biopsy, tissue biopsy, or both. Age younger than 65 years (P = .037), the presence of common mutations (P = .004), and better response to first-line TKI (P = .023) were correlated with T790M positivity. T790M detection was associated with higher number of new progressing sites (P = .04), liver progression (P = .002), and a lower frequency of lung metastases (P = .027). When serial liquid biopsies were performed (N = 15), an oligoprogressive disease was correlated with a negative test outcome, whereas 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.
Authors: Marzia Del Re; Federico Cucchiara; Iacopo Petrini; Stefano Fogli; Antonio Passaro; Stefania Crucitta; Ilaria Attili; Filippo De Marinis; Antonio Chella; Romano Danesi Journal: ESMO Open Date: 2020-08
Authors: Justin D Finkle; Hala Boulos; Terri M Driessen; Christine Lo; Richard A Blidner; Ashraf Hafez; Aly A Khan; Ariane Lozac'hmeur; Kelly E McKinnon; Jason Perera; Wei Zhu; Afshin Dowlati; Kevin P White; Robert Tell; Nike Beaubier Journal: NPJ Precis Oncol Date: 2021-07-02