Metastatic EGFR-Mutant Lung Adenocarcinoma Patients: A Safety and Efficacy Analysis of First- and Third-Generation EGFR-TKIs

• Suha Ali Hammed

  Medical Oncology Department, Aljawad oncology Center, Baghdad, Iraq , Medical Oncology Department, Aljawad oncology Center, Baghdad, Iraq

• Alaa Fadhil Alwan

  The National Center of Hematology Mustansiriyah University, Baghdad, Iraq , Mustansiriyah University

In the context of metastatic non-small cell lung cancer (NSCLC), the phenomenon of resistance to therapeutic interventions is a prevalent occurrence, particularly in cases involving tumors that harbor epidermal growth factor receptor (EGFR) mutations. Tyrosine kinase inhibitors (TKIs) directed at the epidermal growth factor receptor have transformed first-line care. The objective of this study is to compare the safety and effectiveness of first-generation (gefitinib) versus third-generation (osimertinib) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in treatment-naïve patients with metastatic epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma. A cross-sectional cohort study was conducted at the Oncology Teaching Hospital in Baghdad from 2023 to 2024. The study included 40 adults with molecularly confirmed epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), who received first-line gefitinib or osimertinib treatment. The tumor response was evaluated using the RECIST v1.1 criteria at the three-cycle interval, and the adverse events (AEs) were assessed according to the CTCAE v4.03 scale. The PFS was estimated using Kaplan–Meier methods. The study demonstrated that osimertinib resulted in a substantially longer mean progression-free survival (18.2 months; 95% CI: 13.97–25.03) in comparison to gefitinib (7.1 months; 95% CI: 4.54–12.46; p<0.00000001). A complete response was observed more frequently in the osimertinib group (85% vs. 40%). Dermatologic and gastrointestinal AEs were more prevalent in patients treated with gefitinib, while interstitial lung disease was reported exclusively in cases involving osimertinib. Osimertinib exhibited superior efficacy with a more manageable safety profile compared with gefitinib and should be preferred as first-line therapy in eligible patients with metastatic EGFR-mutant NSCLC.

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