Impact of Specific Epidermal Growth Factor Receptor ( EGFR ) Mutations and Clinical Characteristics on Outcomes After Treatment With EGFR Tyrosine Kinase Inhibitors Versus Chemotherapy in EGFR -Mutant Lung Cancer: A Meta-Analysis
Abstract
Purpose: We examined the impact of different epidermal growth factor receptor (EGFR) mutations and clinical characteristics on progression-free survival (PFS) in patients with advanced EGFR-mutated non–small-cell lung cancer treated with EGFR tyrosine kinase inhibitors (TKIs) as first-line therapy. Patients and Methods: This meta-analysis included randomized trials comparing EGFR TKIs with chemotherapy. We calculated hazard ratios (HRs) and 95% CIs for PFS for the trial population and prespecified subgroups and calculated pooled estimates of treatment efficacy using the fixed-effects inverse-variance-weighted method. All statistical tests were two sided. Results: In seven eligible trials (1,649 patients), EGFR TKIs, compared with chemotherapy, significantly prolonged PFS overall (HR, 0.37; 95% CI, 0.32 to 0.42) and in all subgroups. For tumors with exon 19 deletions, the benefit was 50% greater (HR, 0.24; 95% CI, 0.20 to 0.29) than for tumors with exon 21 L858R substitution (HR, 0.48; 95% CI, 0.39 to 0.58; P interaction < .001). Never-smokers had a 36% greater benefit (HR, 0.32; 95% CI, 0.27 to 0.37) than current or former smokers (HR, 0.50; 95% CI, 0.40 to 0.63; P interaction < .001). Women had a 27% greater benefit (HR, 0.33; 95% CI, 0.28 to 0.38) than men (HR, 0.45; 95% CI, 0.36 to 0.55; treatment-sex interaction P = .02). Performance status, age, ethnicity, and tumor histology did not significantly predict additional benefit from EGFR TKIs. Conclusion: Although EGFR TKIs significantly prolonged PFS overall and in all subgroups, compared with chemotherapy, greater benefits were observed in those with exon 19 deletions, never-smokers, and women. These findings should enhance drug development and economic analyses, as well as the design and interpretation of clinical trials.
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A meta-analysis including seven randomized trials comparing EGFR-TKI to platinum doublet chemotherapy found that the hazard ratio of progression-free survival for Del19 tumors was 0.24 (95% CI 0.20-0.29) and for L858R tumors was 0.48 (95% CI 0.39-0.58); the Del19 hazard ratio was 50% greater.
“The study revealed that the HR of PFS for tumors with Del19 was 50% greater (HR 0.24, 95% CI 0.20–0.29) than for tumors with L858R (HR 0.48, 95% CI 0.39–0.58).51”
From Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy (2016) · cites this paper as [51]
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- Authors
- Lee, C. K., Wu, Y.-L., Ding, P. N., Lord, S. J., Inoue, A., Zhou, C., Mitsudomi, T., Rosell, R., Pavlakis, N., Links, M., Gebski, V., Gralla, R. J., & Yang, J. C.-H.
- Affiliations
- The University of Sydney (AU)
- Tongji University (CN)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2015-06-10
- Volume
- 33
- Issue
- 17
- Pages
- 1958-1965
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2130256619
- Semantic Scholar
- edb0b3cb073db6ae9aae563d7e6150b9b18fcaa5
- Cited by
- 327
- References
- 6
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 18 · 2023: 25 · 2022: 28 · 2021: 29 · 2020: 37 · 2019: 37 · 2018: 33 · 2017: 40 · 2016: 41 · 2015: 11
- FWCI
- 7.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- EGFR-mutant non-small cell lung cancer, EGFR tyrosine kinase inhibitors, EGFR mutation, exon 19 deletion, progression-free survival, never smokers, sex differences, first-line therapy, chemotherapy comparison, predictive biomarkers, treatment response prediction, subgroup analysis, performance status, age, ethnicity, tumor histology, smoking
- MeSH terms
- Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Enzyme Inhibitors, Female, Humans, Lung Neoplasms, Male, Mutation, Protein-Tyrosine Kinases, Risk Factors, Smoking, Odds Ratio, Treatment Outcome, Disease-Free Survival, ErbB Receptors
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