Osimertinib vs. Afatinib in 1L therapy of atypical EGFR-mutated metastatic non-small cell lung cancer (mNSCLC): A multi-institution, real-world survival analysis

作者：Adam Barsouk, Omar Elghawy, Alex Watts, Lauren Reed-Guy, William Tompkins, Krishna Chandrasekhara, Connor B. Grady, Wade T. Iams, Fangdi Sun, Geoffrey Liu, Devalben Patel, Jorgé Nieva, Kristen A. Marrone, Vamsidhar Velcheti, Stephen V. Liu, Tejas Patil, Jared Weiss, William Schwartzman, Liza C. Villaruz, Amanda Hermann, Dara L. Aisner, Wei‐Ting Hwang, D. Ross Camidge, Lova Sun, Aditi Singh, Roger B. Cohen, Charų C. Aggarwal, Corey J. Langer, Melina E. Marmarelis · 发表于：Lung Cancer · 年份：2025 · DOI：10.1016/j.lungcan.2025.108551 · 被引用次数：6 · 研究领域：Lung Cancer Treatments and Mutations、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Melanoma and MAPK Pathways

BACKGROUND: Data are limited on the efficacy of different TKIs for patients with atypical EGFR-mutated (AM) mNSCLC, a heterogeneous group excluding classical mutations (CM) L858R and exon19del. In our previous single-institution analysis, AM patients had longer survival with osimertinib than afatinib, but outcomes for patients with specific mutations could not be compared due to sample size. METHODS: We performed a multi-institution, retrospective survival analysis of atypical EGFR mutated (AM) mNSCLC patients treated with 1L osimertinib or afatinib between 2015-2021 at 12 US institutions. Time to discontinuation (TTD) and overall survival (OS) were estimated using Kaplan-Meier curves and compared using log rank tests between treatment or mutation groups. RESULTS: Among 52 patients identified, 32 (62 %) were treated with osimertinib and 20 (38 %) with afatinib. 20 had mutations in G719X (38 %), 12 in L861Q (23 %), and 5 in S768I (10 %). 34(65 %) had compound mutations: 20(62 %) had AM + CM, and 14(38 %) had ≥ 2 AMs. Among G719X (n = 20), afatinib was associated with longer time to discontinuation (TTD) (log-rank: p = 0.047) and longer OS (p = 0.043) vs. osimertinib. Median TTD (mTTD) was 20.3 m[95 %CI 7.3-24.2] and 9.4[1.7-14.0], respectively. For L861Q (n = 12), osimertinib was associated with longer TTD vs. afatinib (p = 0.004), with no statistical difference in OS (p = 0.215). mTTD was 7.2 m[2.2-12.3] and 1.3[0-3.1], respectively. In AM + CM (n = 20), osimertinib was assoc...