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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Afatinib in the treatment of EGFR mutation-positive NSCLC--a network meta-analysis
Sanjay Popat1, Tony Mok2, James Chih-Hsin Yang3
1Royal Marsden Hospital, London, UK.
Objectives:
Epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is a specific lung cancer subtype characterized by sensitivity to treatment with EGFR tyrosine kinase inhibitors (TKIs). Two reversible EGFR TKIs (gefitinib, erlotinib) and the irreversible ErbB family blocker afatinib are currently approved for treatment of EGFR mutation-positive NSCLC, but no head-to-head trials have been reported to date. We aimed to assess the relative efficacy of the three drugs by conducting a network meta-analysis (NMA).
Materials And Methods:
A systematic literature review was conducted to identify all the available evidence. Outcomes of interest were progression-free survival (PFS) and overall survival. For PFS, results by investigator review were considered as not all trials assessed PFS independently. Results were analyzed using Bayesian methods.
Results:
The literature search identified 246 articles that were assessed for eligibility, of which 21 studies were included in the NMA, including eight trials performed in an EGFR mutation-positive population. The estimated PFS HR (95% credible interval, CrI) for afatinib compared with gefitinib was 0.70 (0.40-1.16) and compared with erlotinib was 0.86 (0.50-1.50) in the total population. The estimated probability of being best for afatinib over all other treatments for PFS was 70% versus 27% for erlotinib and 3% for gefitinib; the estimated probability of chemotherapy being the best treatment was 0%. Estimated HR (95% CrI) in patients with common mutations was 0.73 (0.42-1.24) for afatinib compared with erlotinib and 0.60 (0.34-0.99) for afatinib compared with gefitinib. OS findings were not significantly different between treatments.
Conclusions:
In the absence of direct head-to-head trial data comparing efficacy between the three EGFR TKIs, our analysis suggests that afatinib is a viable treatment alternative to erlotinib or gefitinib in terms of PFS. A direct trial-based comparison of the efficacy of these agents is warranted to clarify their relative benefits.
Insights
Afatinib shows promise for improving progression-free survival (PFS) in EGFR mutation-positive non-small cell lung cancer (NSCLC) compared to gefitinib or erlotinib. Further head-to-head trials are needed to confirm these findings for EGFR tyrosine kinase inhibitors (TKIs).
Area of Science:
- Oncology
- Pharmacology
- Biostatistics
Background:
- Epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is a distinct subtype sensitive to EGFR tyrosine kinase inhibitors (TKIs).
- Gefitinib, erlotinib (reversible TKIs), and afatinib (irreversible ErbB family blocker) are approved for EGFR-mutation positive NSCLC.
- No direct head-to-head trials comparing these EGFR TKIs currently exist.
Purpose of the Study:
- To conduct a network meta-analysis (NMA) assessing the relative efficacy of gefitinib, erlotinib, and afatinib.
- To evaluate progression-free survival (PFS) and overall survival (OS) for these EGFR TKIs in EGFR mutation-positive NSCLC.
- To provide insights into treatment selection in the absence of direct comparative trial data.
Main Methods:
- Systematic literature review to identify relevant studies.
- Inclusion of 21 studies in the NMA, with eight focusing on EGFR mutation-positive populations.
- Bayesian methods were employed for data analysis, focusing on PFS and OS outcomes.
Main Results:
- Afatinib demonstrated a favorable trend in PFS compared to gefitinib (HR 0.70) and erlotinib (HR 0.86) in the overall population.
- Afatinib had a 70% probability of being the best treatment for PFS, outperforming erlotinib (27%) and gefitinib (3%).
- In patients with common mutations, afatinib showed improved PFS compared to gefitinib (HR 0.60) and erlotinib (HR 0.73). OS did not differ significantly.
Conclusions:
- Network meta-analysis suggests afatinib is a viable alternative to erlotinib or gefitinib for improving PFS in EGFR mutation-positive NSCLC.
- The study highlights the need for direct head-to-head trials to definitively establish the relative efficacy of these EGFR TKIs.
- Findings support afatinib as a potential treatment option, particularly for progression-free survival benefits.
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