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Advisor(s)
Abstract(s)
Osimertinib efficacy in pre-treated patients with epidermal growth factor receptor (EGFR) T790M-mutated non-small cell lung cancer (NSCLC) has been demonstrated in clinical trials, but real-world data, particularly regarding resistance profile, remains limited. This study aims to analyze the resistance mechanisms acquired after treatment with Osimertinib. Clinical outcomes and molecular results from re-biopsies at the time of osimertinib progression of EGFR T790M-mutated NSCLC patient were analyzed. Twenty-one patients with stage IV adenocarcinoma were included [median 69 years; 57.1% female; 85.7% never-smokers; 23.8% ECOG performance status (PS) ≥2]. Median PFS and OS were 13.4 (95% CI: 8.0–18.9) and 26.4 (95% IC: 8.9–43.8) months, respectively. At the time of analysis, 10 patients had tumor progression (47.6%). T790M loss occurred in 50%, being associated with earlier progression (median PFS 8.1 vs. 21.4 months, p = 0.011). Diverse molecular alterations were identified, including C797S mutation (n = 1), PIK3CA mutation (n = 2), MET amplification (n = 1), CTNNB1 mutation (n = 1), and DCTN1-ALK fusion (n = 1). Histological transformation into small cell carcinoma occurred in one patient. This real-world life study highlights the relevance of re-biopsy at the time of disease progression, contributing to understand resistance mechanisms and to guide treatment strategies.
Description
Keywords
Non-small cell lung cancer EGFR T790M mutation Osimertinib Resistance Real-world data Next generation sequencing
Citation
Fernandes, M. G. O., Sousa, C., Jacob, M., Almeida, L., Santos, V., Araújo, D., Novais Bastos, H., Magalhães, A., Cirnes, L., Moura, C. S., Queiroga, H., Cruz-Martins, N., & Hespanhol, V. (2021). Resistance Profile of Osimertinib in Pre-treated Patients With EGFR T790M-Mutated Non-small Cell Lung Cancer. Frontiers in Oncology, 11, 1–7. https://doi.org/doi.org/10.3389/fonc.2021.602924
Publisher
Frontiers