N.N. Petrov National Medical Research Center of Oncology, Ministry of Public Health of the Russian Federation, Saint-Petersburg, Russia.
N.P. Napalkov Saint Petersburg Clinical Research & Practical Centre for Specialized Types of Medical Care (Oncological), Saint-Petersburg, Russia.
Future Oncol. 2024;20(31):2397-2407. doi: 10.1080/14796694.2024.2386925. Epub 2024 Sep 4.
Administration of single-agent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a standard treatment option for metastatic non-small cell lung carcinomas with EGFR exon 19 deletions (ex19del) and L858R substitutions. However, there is a significant interpatient heterogeneity with regard to the degree of the response and its duration. Patients with EGFR ex19del mutation, TP53 wild-type, good performance status, low tumor burden and no circulating tumor DNA (ctDNA) at baseline have the best chances to derive pronounced benefit from TKI therapy. In contrast, subjects with EGFR L858R substitution, mutated TP53, poor overall condition, high tumor volume and detectable ctDNA are generally poor responders to EGFR inhibitors. ctDNA dynamics in the first days or weeks of treatment allows reliable identification of patients, who are very unlikely to derive clinically meaningful benefit from single-agent TKIs. These patients are candidates for clinical trials, which may involve the addition of chemotherapy and antiangiogenic drugs to patients, who failed to achieve immediate benefit from TKI monotherapy.
单药表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）的给药是具有 EGFR 外显子 19 缺失（ex19del）和 L858R 取代的转移性非小细胞肺癌的标准治疗选择。然而，在反应的程度和持续时间方面存在显著的个体间异质性。具有 EGFR ex19del 突变、TP53 野生型、良好的表现状态、低肿瘤负担和基线时无循环肿瘤 DNA（ctDNA）的患者，最有可能从 TKI 治疗中获得显著获益。相比之下，具有 EGFR L858R 取代、突变型 TP53、总体状况不佳、高肿瘤体积和可检测到 ctDNA 的患者，通常对 EGFR 抑制剂反应不佳。治疗的最初几天或几周内的 ctDNA 动态变化可以可靠地识别那些非常不可能从单药 TKI 治疗中获得临床意义获益的患者。这些患者是临床试验的候选者，这些临床试验可能涉及在 TKI 单药治疗未立即获益的患者中加入化疗和抗血管生成药物。
