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Favorable survival outcomes in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer sequentially treated with a tyrosine kinase inhibitor and osimertinib in a real-world setting.

Authors :
Kraskowski, Oliver
Stratmann, Jan A.
Wiesweg, Marcel
Eberhardt, Wilfried
Metzenmacher, Martin
Schmid, Kurt W.
Herold, Thomas
Schildhaus, Hans-Ulrich
Darwiche, Kaid
Aigner, Clemens
Stuschke, Martin
Laue, Katharina
Zaun, Gregor
Kasper, Stefan
Hense, Jörg
Sebastian, Martin
Schuler, Martin
Pogorzelski, Michael
Source :
Journal of Cancer Research & Clinical Oncology; Sep2023, Vol. 149 Issue 11, p9243-9252, 10p
Publication Year :
2023

Abstract

Purpose: EGFR tyrosine kinase inhibitor (TKI) therapy in EGFR-mutated lung cancer is limited by acquired resistance. In half of the patients treated with first/second-generation (1st/2nd gen) TKI, resistance is associated with EGFR p.T790M mutation. Sequential treatment with osimertinib is highly active in such patients. Currently, there is no approved targeted second-line option for patients receiving first-line osimertinib, which thus may not be the best choice for all patients. The present study aimed to evaluate the feasibility and efficacy of a sequential TKI treatment with 1st/2nd gen TKI, followed by osimertinib in a real-world setting. Methods: Patients with EGFR-mutated lung cancer treated at two major comprehensive cancer centers were retrospectively analyzed by the Kaplan–Meier method and log rank test. Results: A cohort of 150 patients, of which 133 received first-line treatment with a first/second gen EGFR TKI, and 17 received first-line osimertinib, was included. Median age was 63.9 years, 55% had ECOG performance score of ≥ 1. First-line osimertinib was associated with prolonged progression-free survival (P = 0.038). Since the approval of osimertinib (February 2016), 91 patients were under treatment with a 1st/2nd gen TKI. Median overall survival (OS) of this cohort was 39.3 months. At data cutoff, 87% had progressed. Of those, 92% underwent new biomarker analyses, revealing EGFR p.T790M in 51%. Overall, 91% of progressing patients received second-line therapy, which was osimertinib in 46%. Median OS with sequenced osimertinib was 50 months. Median OS of patients with p.T790M-negative progression was 23.4 months. Conclusion: Real-world survival outcomes of patients with EGFR-mutated lung cancer may be superior with a sequenced TKI strategy. Predictors of p.T790M-associated resistance are needed to personalize first-line treatment decisions. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01715216
Volume :
149
Issue :
11
Database :
Complementary Index
Journal :
Journal of Cancer Research & Clinical Oncology
Publication Type :
Academic Journal
Accession number :
167361917
Full Text :
https://doi.org/10.1007/s00432-023-04839-3