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Updated: Dec 30, 2025
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Front-line Therapy in Advanced Non-Small Cell Lung Cancer With Sensitive Epidermal Growth Factor Receptor Mutations:
Xu-Yuan Li1, Jia-Zhou Lin2, Shu-Han Yu1
1Department of Medical Oncology, Shantou Central Hospital, Shantou, China.
Purpose:
Several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were firmly established as front-line treatment for non-small cell lung cancer (NSCLC) that harbored an activating EGFR mutation. Gefitinib or erlotinib was considered the standard of care. TKI-based combination therapy has been investigated and has shown encouraging results.
Methods:
The PubMed and EMBASE databases, the Cochrane Central Register of Controlled Trials, and meeting abstracts were screened for relevant studies between January 2000 and February 2019. Prospective randomized controlled trials were included that investigated EGFR TKIs (alone or in combination) in untreated patients with NSCLC whose tumors had sensitive EGFR mutations. A frequentist random effects network meta-analysis model was conducted to assess objective response rate, progression-free survival, and overall survival. P-score was used to rank treatment effects.
Findings:
Seventeen trials involving 9 treatments and 4373 patients were included. Heterogeneity existed in the network analysis. For progression-free survival, the top 3 treatments were osimertinib, standard of care plus chemotherapy, and standard of care plus bevacizumab; corresponding p-scores were 0.88, 0.79, and 0.75, respectively. For overall survival, the top 3 treatments were standard of care plus chemotherapy, osimertinib, and dacomitinib; corresponding p-scores were 0.89, 0.85, and 0.64. TKI-based combination therapy caused more toxicity than a TKI alone.
Implications:
Osimertinib seemed to be a better option as upfront therapy for EGFR-mutant NSCLC in terms of efficacy and tolerability.
Insights
Osimertinib shows promise as a first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC), offering improved efficacy and tolerability compared to other therapies. This finding aids in selecting optimal upfront treatment strategies for NSCLC patients.
Area of Science:
- Medical Oncology
- Pharmacological Research
- Clinical Trial Analysis
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard first-line treatments for EGFR-mutated non-small cell lung cancer (NSCLC).
- Established TKIs like gefitinib and erlotinib form the current standard of care.
- Emerging TKI-based combination therapies demonstrate encouraging preliminary results.
Purpose of the Study:
- To compare the efficacy and safety of various EGFR TKI-based treatments for untreated, EGFR-mutated NSCLC.
- To identify optimal upfront therapeutic strategies through network meta-analysis.
Main Methods:
- A systematic literature search of PubMed, EMBASE, Cochrane Library, and meeting abstracts (Jan 2000 - Feb 2019).
- Inclusion of prospective randomized controlled trials investigating EGFR TKIs alone or in combination.
- Application of a frequentist random effects network meta-analysis to evaluate objective response rate, progression-free survival (PFS), and overall survival (OS).
Main Results:
- Seventeen trials with 4373 patients and 9 treatment arms were analyzed.
- For PFS, osimertinib ranked highest (p-score 0.88), followed by standard of care plus chemotherapy (0.79) and standard of care plus bevacizumab (0.75).
- For OS, standard of care plus chemotherapy ranked highest (p-score 0.89), followed by osimertinib (0.85) and dacomitinib (0.64). Combination therapies showed increased toxicity.
Conclusions:
- Osimertinib emerges as a potentially superior upfront therapy for EGFR-mutant NSCLC, balancing efficacy and tolerability.
- The findings support further investigation into osimertinib as a preferred first-line option.
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