Tyrosine Kinase Inhibitor Activity in Patients with NSCLC Harboring Uncommon EGFR Mutations: A Retrospective International Cohort Study (UpSwinG). (11th March 2022)

• Record Type: Journal Article
• Authors: Popat, Sanjay; Hsia, Te-Chun; Hung, Jen-Yu; Jung, Hyun Ae; Shih, Jin-Yuan; Park, Cheol Kyu; Lee, Seung Hyeun; Okamoto, Tatsuro; Ahn, Hee Kyung; Lee, Yong Chul; Sato, Yuki; Lee, Sung Sook; Mascaux, Celine; Daoud, Hasan; Märten, Angela; Miura, Satoru
• Is Part Of: Oncologist. Volume 27:Number 4(2022)
• Page Start: 255
• Page End: 265
• Publication Date: 2022-03-11
• Subjects: EGFR -- uncommon EGFR mutations -- afatinib -- osimertinib -- gefitinib -- erlotinib; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1093/oncolo/oyac022
• Languages: English
• ISSNs: 1083-7159

Abstract

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. Abstract : This article reports partial findings of the UpSwinG study, focusing on a cohort of patients with tumors harboring uncommon EGFR mutations who received first- or second-line EGFR tyrosine kinase inhibitor treatment.