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      Overall survival in advanced epidermal growth factor receptor mutated non-small cell lung cancer using different tyrosine kinase inhibitors in The Netherlands: a retrospective, nationwide registry study

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          Summary

          Background

          Clinical guidelines advise osimertinib as preferred first line treatment for advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) with deletions in exon 19 (del19) or exon 21 L858R mutation. However, for first-line osimertinib the real world overall survival (OS) in mutation subgroups remains unknown. Therefore, the aim of this study was to evaluate the real-world OS of those patients treated with different generations of EGFR-tyrosine kinase inhibitors (TKI), and to identify predictors of survival.

          Methods

          Using real-world data from the Netherlands Cancer Registry (NCR) we assessed patients diagnosed with stage IV NSCLC with del19 or L858R mutation between January 1, 2015, and December 31, 2020, primarily treated with then regularly available TKIs (including osimertinib).

          Findings

          Between January 1, 2015, and December 31, 2020, 57,592 patients were included in the NCR. Within this cohort we identified 1109 patients, 654 (59%) with del19 and 455 (41%) with L858R mutations, respectively; 230 (21%) patients were diagnosed with baseline brain metastases (BM). Patients were treated with gefitinib (19%, 213/1109), erlotinib (42%, 470/1109), afatinib (15%, 161/1109) or osimertinib (24%, 265/1109). Median OS was superior for del19 versus L858R (28.4 months (95% CI 25.6–30.6) versus 17.7 months (95% CI 16.1–19.5), p < 0.001. In multivariable analysis, no difference in survival was observed between various TKIs in both groups. Only in the subgroup of patients with del19 and baseline BM, a benefit was observed for treatment with osimertinib.

          Interpretation

          In this nationwide real-world cohort, survival of Dutch patients with advanced NSCLC and an EGFR del19 mutation was superior versus those harboring an L858R mutation. Osimertinib performed only better as first-line treatment in patients with del19 and BM.

          Funding

          None.

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          Most cited references46

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          Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer

          Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC).
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            Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC

            Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer progression-free survival with osimertinib than with the comparator EGFR-TKIs (hazard ratio for disease progression or death, 0.46). Data from the final analysis of overall survival have not been reported.
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              Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials.

              We aimed to assess the effect of afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label, randomised, phase 3 trials.
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                Author and article information

                Contributors
                Journal
                Lancet Reg Health Eur
                Lancet Reg Health Eur
                The Lancet Regional Health - Europe
                Elsevier
                2666-7762
                06 February 2023
                April 2023
                06 February 2023
                : 27
                : 100592
                Affiliations
                [a ]Department of Respiratory Medicine, Medical Center Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden, Netherlands
                [b ]Department of Research, Comprehensive Cancer Organization, Plesmanlaan 121, 1066 CX, Utrecht, Netherlands
                [c ]Department of Pulmonary Diseases, University Medical Center Groningen and University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, Netherlands
                [d ]Department of Respiratory Medicine, Maastricht University Medical Centre, GROW School for Oncology and Reproduction, P. Debyelaan 25, 6229 HX, Maastricht, Netherlands
                Author notes
                []Corresponding author. Department of Respiratory Medicine, Medical Center Leeuwarden, Henri Dunantweg 2, 8934 AD Leeuwarden, Netherlands. wouter.van.geffen@ 123456mcl.nl
                Article
                S2666-7762(23)00010-8 100592
                10.1016/j.lanepe.2023.100592
                9932646
                36817181
                857a4998-5482-4528-9864-8989bc852c4e
                © 2023 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 November 2022
                : 18 January 2023
                : 19 January 2023
                Categories
                Articles

                non-small cell lung cancer,epidermal growth factor receptor,tyrosine kinase inhibitor

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