Anna Buder1, Maximilian J Hochmair2, Sophia Schwab2, Tatjana Bundalo3, Peter Schenk3, Peter Errhalt4, Romana E Mikes5, Gudrun Absenger6, Kurt Patocka7, Bernhard Baumgartner8, Ulrike Setinek2, Otto C Burghuber2, Helmut Prosch9, Robert Pirker10, Martin Filipits11. 1. Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical Center of Vienna, Vienna, Austria. 2. Department of Respiratory and Critical Care Medicine, and Ludwig Boltzmann Institute of COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna, Austria. 3. Department of Pneumology, LKH Hochegg, Hochegg, Austria. 4. Department of Pneumology, University Hospital Krems, Krems, Austria. 5. Department of Pulmonary Medicine, University Clinic Salzburg, Salzburg, Austria. 6. Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Graz, Austria. 7. Department of Pneumology, Hietzing Hospital, Vienna, Austria. 8. Department of Pneumology, Vöcklabruck Hospital, Vöcklabruck, Austria. 9. Department of Radiology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 10. Division of Oncology, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 11. Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical Center of Vienna, Vienna, Austria. Electronic address: martin.filipits@meduniwien.ac.at.
Abstract
INTRODUCTION: Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non-small-cell lung cancer who have been pre-treated with EGFR-tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine. METHODS: From April 2015 to November 2016, we included 119 patients with advanced EGFR-mutated non-small-cell lung cancer who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital polymerase chain reaction in all patients and by tissue analyses in selected patients. RESULTS: T790M mutations were detected in 85 (93%) patients by analyses of cell-free plasma DNA and in 6 (7%) plasma-negative patients by tumor re-biopsy. Eighty-nine of 91 T790M-positive patients received osimertinib. Median progression-free survival (PFS) was 10.1 months (95% confidence interval [CI]: 8.1-12.1). Median survival was not reached and the 1-year survival was 64%. The response rate was 70% in T790M-positive patients (n = 91) in the intention-to-treat population. PFS trended to be shorter in patients with high T790M copy number (≥10 copies/mL) compared to those with low T790M copy number (<10 copies/mL) (hazard ratio for PFS = 1.72, 95% CI: 0.92-3.2, p = 0.09). A comparable trend was observed for overall survival (hazard ratio for overall survival = 2.16, 95% CI: 0.89-5.25, p = 0.09). No difference in response rate was observed based on T790M copy numbers. CONCLUSION: Plasma genotyping using digital polymerase chain reaction is clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib.
INTRODUCTION: Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non-small-cell lung cancer who have been pre-treated with EGFR-tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine. METHODS: From April 2015 to November 2016, we included 119 patients with advanced EGFR-mutated non-small-cell lung cancer who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital polymerase chain reaction in all patients and by tissue analyses in selected patients. RESULTS: T790M mutations were detected in 85 (93%) patients by analyses of cell-free plasma DNA and in 6 (7%) plasma-negative patients by tumor re-biopsy. Eighty-nine of 91 T790M-positive patients received osimertinib. Median progression-free survival (PFS) was 10.1 months (95% confidence interval [CI]: 8.1-12.1). Median survival was not reached and the 1-year survival was 64%. The response rate was 70% in T790M-positive patients (n = 91) in the intention-to-treat population. PFS trended to be shorter in patients with high T790M copy number (≥10 copies/mL) compared to those with low T790M copy number (<10 copies/mL) (hazard ratio for PFS = 1.72, 95% CI: 0.92-3.2, p = 0.09). A comparable trend was observed for overall survival (hazard ratio for overall survival = 2.16, 95% CI: 0.89-5.25, p = 0.09). No difference in response rate was observed based on T790M copy numbers. CONCLUSION: Plasma genotyping using digital polymerase chain reaction is clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib.
Authors: Pei N Ding; Tara L Roberts; Wei Chua; Therese M Becker; Nicole Caixeiro; Paul de Souza; Bo Gao; Chee K Lee; Malinda Itchins; Helen Westman; Stephen Clarke; Prunella Blinman; Steven Kao; Tom John; Jose L Leal; Victoria J Bray Journal: Transl Lung Cancer Res Date: 2021-04
Authors: Anna Buder; Ellen Heitzer; Julie Waldispühl-Geigl; Sabrina Weber; Tina Moser; Maximilian J Hochmair; Klaus Hackner; Peter Errhalt; Ulrike Setinek; Martin Filipits Journal: Biomolecules Date: 2021-04-21
Authors: Maximilian J Hochmair; Anna Buder; Sophia Schwab; Otto C Burghuber; Helmut Prosch; Wolfgang Hilbe; Agnieszka Cseh; Richard Fritz; Martin Filipits Journal: Target Oncol Date: 2019-02 Impact factor: 4.493