Tyrosine Kinase Inhibitor Activity in Patients with NSCLC Harboring Uncommon EGFR Mutations: A Retrospective International Cohort Study (UpSwinG).

Abstract

BACKGROUND:

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.

PATIENTS AND METHODS:

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).

RESULTS:

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.

CONCLUSION:

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.

• Authors: Sanjay Popat, Te-Chun Hsia, Jen-Yu Hung, Hyun Ae Jung, Jin-Yuan Shih, Cheol Kyu Park, Seung Hyeun Lee, Tatsuro Okamoto, Hee Kyung Ahn, Yong Chul Lee, Yuki Sato, Sung Sook Lee, Celine Mascaux, Hasan Daoud, Angela Märten, Satoru Miura
• Journal: The oncologist (Oncologist) Vol. 27 Issue 4 Pg. 255-265 (04 05 2022) ISSN: 1549-490X [Electronic] England
• PMID: 35274704 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press.

Chemical References

• Protein Kinase Inhibitors
• EGFR protein, human
• ErbB Receptors

Topics

• Aged
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Cohort Studies
• ErbB Receptors
• Humans
• Lung Neoplasms (drug therapy, genetics, pathology)
• Mutation
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Retrospective Studies