First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations
- PMID: 18458038
- DOI: 10.1200/JCO.2007.14.8494
First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations
Erratum in
- J Clin Oncol. 2008 Jul 10;26(20):3472
Abstract
Purpose: Somatic mutations in the epidermal growth factor receptor (EGFR) correlate with increased response in patients with non-small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). The multicenter iTARGET trial prospectively examined first-line gefitinib in advanced NSCLC patients harboring EGFR mutations and explored the significance of EGFR mutation subtypes and TKI resistance mechanisms.
Patients and methods: Chemotherapy-naïve patients with advanced NSCLC with >or= 1 clinical characteristic associated with EGFR mutations underwent direct DNA sequencing of tumor tissue EGFR exons 18 to 21. Patients found to harbor any EGFR mutation were treated with gefitinib 250 mg/d until progression or unacceptable toxicity. The primary outcome was response rate.
Results: Ninety-eight patients underwent EGFR screening and mutations were detected in 34 (35%). EGFR mutations were primarily exon 19 deletions (53%) and L858R (26%) though 21% of mutation-positive cases had less common subtypes including exon 20 insertions, T790M/L858R, G719A, and L861Q. Thirty-one patients received gefitinib. The response rate was 55% (95% CI, 33 to 70) and median progression-free survival was 9.2 months (95% CI, 6.2 to 11.8). Therapy was well tolerated; 13% of patients had grade 3 toxicities including one grade 3 pneumonitis. Two patients with classic activating mutations exhibited de novo gefitinib resistance and had concurrent genetic anomalies usually associated with acquired TKI resistance, specifically the T790M EGFR mutation and MET amplification.
Conclusion: First-line therapy with gefitinib administered in a genotype-directed fashion to patients with advanced NSCLC harboring EGFR mutations results in very favorable clinical outcomes with good tolerance. This strategy should be compared with combination chemotherapy, the current standard of care.
Comment in
-
Molecular selection of patients for first-line treatment of advanced non-small-cell lung cancer with epidermal growth factor inhibitors: not quite ready for prime time.J Clin Oncol. 2008 May 20;26(15):2426-7. doi: 10.1200/JCO.2007.15.4286. Epub 2008 May 5. J Clin Oncol. 2008. PMID: 18458043 No abstract available.
Similar articles
-
A multicenter phase II study to evaluate the efficacy and safety of gefitinib as first-line treatment for Korean patients with advanced pulmonary adenocarcinoma harboring EGFR mutations.Lung Cancer. 2011 Jan;71(1):65-9. doi: 10.1016/j.lungcan.2010.04.005. Lung Cancer. 2011. PMID: 20430469 Clinical Trial.
-
Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy.Lung Cancer. 2007 Jun;56(3):383-9. doi: 10.1016/j.lungcan.2007.01.025. Epub 2007 Mar 26. Lung Cancer. 2007. PMID: 17368623 Clinical Trial.
-
Gefitinib as first-line treatment in elderly epidermal growth factor receptor-mutated patients with advanced lung adenocarcinoma: results of a Nagano Lung Cancer Research Group study.Clin Lung Cancer. 2011 Nov;12(6):387-92. doi: 10.1016/j.cllc.2011.02.004. Epub 2011 May 10. Clin Lung Cancer. 2011. PMID: 21729650 Clinical Trial.
-
Gefitinib as first-line treatment for patients with advanced non-small-cell lung cancer with activating epidermal growth factor receptor mutation: Review of the evidence.Lung Cancer. 2011 Mar;71(3):249-57. doi: 10.1016/j.lungcan.2010.12.008. Epub 2011 Jan 8. Lung Cancer. 2011. PMID: 21216486 Review.
-
Gefitinib as first-line treatment for patients with advanced non-small-cell lung cancer with activating Epidermal Growth Factor Receptor mutation: implications for clinical practice and open issues.Lung Cancer. 2011 Apr;72(1):3-8. doi: 10.1016/j.lungcan.2010.12.009. Epub 2011 Jan 8. Lung Cancer. 2011. PMID: 21216488 Review.
Cited by
-
Comprehensive analysis of clinicopathological profiles in adenosquamous carcinoma of the lung.Am J Transl Res. 2024 Jan 15;16(1):126-135. doi: 10.62347/UXQC3380. eCollection 2024. Am J Transl Res. 2024. PMID: 38322563 Free PMC article.
-
Differential efficacy of tyrosine kinase inhibitors according to the types of EGFR mutations and agents in non-small cell lung cancer: a real-world study.BMC Cancer. 2024 Jan 12;24(1):70. doi: 10.1186/s12885-023-11782-6. BMC Cancer. 2024. PMID: 38216948 Free PMC article.
-
Hope and Challenges: Immunotherapy in EGFR-Mutant NSCLC Patients.Biomedicines. 2023 Oct 28;11(11):2916. doi: 10.3390/biomedicines11112916. Biomedicines. 2023. PMID: 38001917 Free PMC article. Review.
-
Deep neural network for discovering metabolism-related biomarkers for lung adenocarcinoma.Front Endocrinol (Lausanne). 2023 Oct 25;14:1270772. doi: 10.3389/fendo.2023.1270772. eCollection 2023. Front Endocrinol (Lausanne). 2023. PMID: 37955007 Free PMC article.
-
EGFR Mutation Detection in Brazilian Patients With Non-Small-Cell Lung Cancer: Lessons From Real-World Data Scenario of Molecular Testing.JCO Glob Oncol. 2023 Sep;9:e2200426. doi: 10.1200/GO.22.00426. JCO Glob Oncol. 2023. PMID: 37769218 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous