Related Experiment Video
Updated: Jun 27, 2026
A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
Published on: April 6, 2016
Where next for gefitinib in patients with lung cancer?
Fiona Blackhall1, Malcolm Ranson, Nick Thatcher
1Cancer Research UK Department of Medical Oncology, Christie Hospital NHS Trust Manchester, M20 4BX, UK. Fiona.Blackhall@christie-tr.nwest.nhs.uk
Abstract:
Gefitinib belongs to the small-molecule class of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors. It was given conditional approval by the US Food and Drug Administration (FDA) in 2003 for treatment of advanced, chemorefractory non-small-cell lung cancer (NSCLC), but was relabelled for restricted use for patients that were already receiving and benefiting from it after the negative result of the phase III Iressa Survival Evaluation in Advanced Lung Cancer (ISEL) trial. By contrast, erlotinib, another EGFR tyrosine-kinase inhibitor, showed an overall survival benefit compared with placebo and best supportive care in the National Cancer Institute of Canada's BR21 trial, and now has full FDA approval for treatment of patients with NSCLC who have progressed after treatment with chemotherapy. Although the ISEL trial result was negative overall, preplanned subgroup analyses showed a significant overall survival benefit for gefitinib treatment in never-smokers and in patients of Asian origin. Here, we review the clinical experience with gefitinib and, in light of the licensing of erlotinib, address the lessons learned, the ongoing trials, and whether scope remains for clinical development of gefitinib in selected patients.
Insights
Gefitinib, an EGFR inhibitor, showed survival benefits in specific non-small-cell lung cancer patient subgroups despite an overall negative trial. Further development may be possible for selected patients.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor.
- Initially approved for advanced non-small-cell lung cancer (NSCLC), its use was restricted after the ISEL trial.
- Erlotinib, another EGFR inhibitor, gained full FDA approval based on the BR21 trial results.
Purpose of the Study:
- To review clinical experience with gefitinib.
- To compare gefitinib's development with erlotinib's.
- To assess the potential for gefitinib's continued clinical development in select patient populations.
Main Methods:
- Review of clinical trial data, including the ISEL and BR21 trials.
- Analysis of subgroup data from the ISEL trial.
- Comparison of gefitinib and erlotinib efficacy and regulatory status.
Main Results:
- The ISEL trial did not show overall survival benefit for gefitinib.
- Subgroup analyses of the ISEL trial indicated a survival benefit for never-smokers and Asian patients.
- Erlotinib demonstrated overall survival benefit in NSCLC patients post-chemotherapy.
Conclusions:
- Despite overall negative results, gefitinib shows promise in specific NSCLC subgroups.
- Lessons learned from gefitinib and erlotinib inform ongoing EGFR inhibitor development.
- Further clinical development of gefitinib may be warranted for selected NSCLC patients.
More Related Videos
09:38Establishing 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
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
