Tyrosine Kinase Inhibitor Activity in Patients with NSCLC Harboring Uncommon EGFR Mutations: A Retrospective International Cohort Study (UpSwinG).
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ICR Author
Author
Popat, S
Hsia, T-C
Hung, J-Y
Jung, HA
Shih, J-Y
Park, CK
Lee, SH
Okamoto, T
Ahn, HK
Lee, YC
Sato, Y
Lee, SS
Mascaux, C
Daoud, H
Märten, A
Miura, S
Type
Journal Article
Metadata
Show full item recordAbstract
<h4>Background</h4>Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are standard of care for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) with common mutations (Del19 or L858R); however, 7%-23% of NSCLC tumors harbor uncommon EGFR mutations. These mutations are highly heterogeneous, and developments in detection techniques are helping to identify mutations with little or no clinical data.<h4>Patients and methods</h4>In this retrospective, global, multi-center study (NCT04179890), existing health records were identified for consecutive EGFR TKI-naïve patients with uncommon EGFR mutations (T790M, ex20ins, major uncommon [G719X, L861Q, or S768I], or "other" mutations; compound mutations) treated with erlotinib, gefitinib, afatinib, or osimertinib in first or second line. Endpoints included time-to-treatment failure (TTF), objective response rate (ORR), and overall survival (OS).<h4>Results</h4>Overall, 246 patients (median age: 69.5 years; Asian: 84%) were included from 9 countries. Most patients (92%) received an EGFR TKI as first-line therapy; 54%, 43% and 3% received afatinib, first-generation TKIs, and osimertinib, respectively. Median TTF and OS with EGFR TKIs were 9.9 and 24.4 months; ORR was 43%. In patients treated with first-line chemotherapy (n = 20), median TTF and ORR were 6.6 months and 41%. Outcomes were most favorable in patients with major uncommon or compound mutations. Overall, TTF was 11.3 months with afatinib and 8.8 months with first-generation EGFR TKIs across mutation categories. In most mutation categories, median OS was >2 years.<h4>Conclusion</h4>In a real-world setting, EGFR TKIs were the preferred treatment option in patients with uncommon EGFR mutations; strongest outcomes were seen in patients with major uncommon and compound mutations.
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Subject
Humans
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Protein Kinase Inhibitors
Retrospective Studies
Cohort Studies
Mutation
Aged
ErbB Receptors
Research team
Thoracic Oncology
Language
eng
Date accepted
2021-12-03
Citation
The oncologist, 2022, 27 (4), pp. 255 - 265