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: Clinical Lung Cancer

A. Dal Maso, M. Lorenzi, E. Roca, S. Pilotto, M. Macerelli, V. Polo, F.L. Cecere, A. Del Conte, G. Nardo, V. Buoro, D. Scattolin, S. Monteverdi, L. Urso, E. Zulato, S. Frega, L. Bonanno, S. Indraccolo, F. Calabrese, P. Conte, G. Pasello

Research output: Contribution to journalArticlepeer-review

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. © 2019 Elsevier Inc. Clinical features and disease course of patients with epidermal growth factor receptor (EGFR)-mutant non–small-cell lung cancer progressing to first-line EGFR-tyrosine kinase inhibitors might be heterogeneous. Age younger than 65, common EGFR mutations, overall response, and typical progression pattern might predict the T790M-positive status. Serial liquid biopsies during treatment could be useful in this population, especially when tissue rebiopsy is not feasible. © 2019 Elsevier Inc.
Original languageEnglish
Pages (from-to)1
Number of pages17
JournalClin. Lung Cancer
Volume21
Issue number1
DOIs
Publication statusPublished - 2020

Keywords

  • Acquired resistance
  • EGFR T790M mutation
  • Epidermal growth factor receptor
  • Non-small cell lung cancer
  • Tyrosine kinase inhibitors
  • afatinib
  • erlotinib
  • gefitinib
  • adult
  • aged
  • Article
  • cancer patient
  • clinical feature
  • disease exacerbation
  • female
  • gene mutation
  • human
  • human tissue
  • liquid biopsy
  • liver metastasis
  • lung metastasis
  • major clinical study
  • male
  • non small cell lung cancer
  • observational study
  • outcome assessment
  • retrospective study
  • systemic disease

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