Comparative outcome assessment of epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of advanced non-small-cell lung cancer: a network meta-analysis

Abstract

IntroductionTyrosine kinase inhibition of the epidermal growth factor receptor (EGFR) is the standard in the first line treatment of patients with advanced non-small–cell lung cancer (NSCLC) harbouring EGFR activating mutations. Here we aim to discern efficacy and toxicity measures through a meta-analysis of published studies that could aid treatment selection.Materials And MethodsWe performed a meta-analysis of the main randomized clinical trials evaluating the currently approved EGFR-TKIs in first-line of treatment of EGFR-positive advanced NSCLC. Cochrane guidelines were used for statistical analysis.Results3,179 patients were included. All EGFR TKIs showed improved outcomes with respect to ORR and PFS when compared to standard platinum-doublet chemotherapy. Comparative ORR for gefitinib, erlotinib and afatinib were 52.1%, 67.3% and 61.6% respectively. HRs for PFS were 0.62 (95% CI, 0.38–1.00) for gefitinib, 0.28 (95% CI, 0.17–0.45) for erlotinib and 0.40 (95% CI, 0.20–0.83) for afatinib. HRs for OS were not statistically significant for any agent.ConclusionsOur results suggest similar clinical efficacy and higher toxicity of Afatinib treatment. As this still remains the agent with best CSF penetration, we suggest its use is limited to patients presenting with brain metastasis. We suggest the use of Gefitinib in patients without CNS involvement. Faced with the impossibility to dose-reduce Gefitinib, Erlotinib represents a tolerable and effective alternative to Afatinib and Gefitinib if response to EGFR inhibition is considered still effective.

MiR‐873 inhibition enhances gefitinib resistance in non‐small cell lung cancer cells by targeting glioma‐associated oncogene homolog 1

“…However, gefitinib will develop resistance in cancer during its application. Recently, a large number of articles have reported gefitinib resistance in NSCLC cells . Herein, we explored the role of miR‐873 in gefitinib resistance in PC9 cells.…”

“…Recently, a large number of articles have reported gefitinib resistance in NSCLC cells. [40][41][42] Herein, we explored the role of miR-873 in gefitinib resistance in PC9 cells.…”

Targeting human epidermal growth factor receptor 2 enhances radiosensitivity and reduces the metastatic potential of Lewis lung carcinoma cells

“…For EGFR mutated NSCLC, EGFR tyrosine kinase inhibitors (TKIs) including afatinib and erlotinib show higher response rates and longer progression-free survival than platinum-based chemotherapy [10]. Afatinib covalently binds to EGFR, HER2, and HER4, and irreversibly inhibits tyrosine kinase autophosphorylation and downregulates ErbB signaling.…”

<p>Cost-Effectiveness Analysis Of EGFR Mutation Testing And Afatinib Versus Gemcitabine-Cisplatin As First-Line Therapy For Advanced Non-Small-Cell Lung Cancer In China</p>

“…First- and second-generation EGFR-TKIs, such as gefitinib, erlotinib, afatinib and osimertinib, are approved first-line treatments by FDA. As illustrated by the results of several randomized clinical trials, these regimens achieve higher response rates, longer progression-free survival (PFS), and a lower incidence of severe adverse effects than platinum-based chemotherapy in a population harboring EGFR mutation 10–12…”