Epidermal growth factor receptor-mutated lung carcinomas with insufficient response to epidermal growth factor receptor inhibitors

• Published in: Future oncology (London, England) Vol. 20; no. 31; pp. 2397 - 2407
• Main Authors: Moiseenko, Fedor, Kuligina, Ekaterina, Elsakova, Ekaterina, Imyanitov, Evgeny
• Format: Journal Article
• Language: English
• Published: England 2024
• Subjects: Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Circulating Tumor DNA - blood; Circulating Tumor DNA - genetics; Drug Resistance, Neoplasm - genetics; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Mutation; Protein Kinase Inhibitors - therapeutic use; Treatment Outcome; lung cancer; tyrosine kinase inhibitors; targeted therapy; EGFR mutations; prognostic factors; non–small cell lung carcinoma
• ISSN: 1479-6694; 1744-8301; 1744-8301
• DOI: 10.1080/14796694.2024.2386925

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.