Specifying the choice of EGFR-TKI based on brain metastatic status for advanced NSCLC with EGFR p.L861Q mutation

作者：Lanlan Pang, Weitao Zhuang, Junjun Li, Bin Li, Yi-Hua Huang, Jun Liao, Meng-di Li, Li Zhang, Wenfeng Fang · 发表于：Neoplasia · 年份：2024 · DOI：10.1016/j.neo.2024.101073 · 被引用次数：3 · 研究领域：Lung Cancer Treatments and Mutations、HER2/EGFR in Cancer Research、Advanced Breast Cancer Therapies

In-depth insight into the genomic features of the uncommon EGFR p.L861Q mutant NSCLC is scarcely performed, and no consensus on the preferred treatment strategy has been established. Moreover, the therapeutic implications of EGFR-TKI stratified by clinical and molecular features remained largely unknown. A multi-center NGS database comprising 44,993 NSCLC samples was utilized for the genomic landscape profiling of EGFR p.L861Q mutation. Furthermore, a real-world cohort of 207 patients harboring EGFR p.L861Q mutation with complete treatment history was curated for comprehensive clinical analysis. L861Q is prevalent in approximately 2.1% of EGFR-mutated NSCLC and is typically co-mutated with EGFR p.G719X on the same allele (20%) and exhibits co-occurrent EGFR copy number amplification in approximately 17% of cases. In the first-line setting, afatinib and third-generation EGFR-TKI have been shown to yield notably superior treatment outcomes compared to first-generation EGFR-TKI (1 st vs.2 nd vs.3 rd generations, ORR: 15.8% vs.56.5% vs.46.7%, P =0.01; median PFS: 6.4 vs.13.5 vs.15.1 months, P =0.002). This finding consistently held for patients without CNS metastases (1 st vs.2 nd vs.3 rd generations, median PFS:6.0 vs.18.2 vs.14.1 months, P =0.003). In contrast, third-generation EGFR-TKI demonstrated superior efficacy compared to afatinib or first-generation TKI among the subgroup of brain metastasis (Pooled 1 st /2 nd -generation vs.3 rd -generation TKI, brain ORR:0.00% vs.33.3...